Monday, December 13, 2010

Role of FADH2/NADH flux ratio in peroxisome evolution..!

Dr. Dave Speijer from University of Amsterdam has authored an Hypothesis article under "Insights & Perspectives" in BioEssays Journal.


According to Dr.Speijer, F/N Flux ratio (ratio of electrons passing through FADH2 and NADH) was the critical factor which led to acquisition of membrane bound organelle peroxisome that became specialized in beta oxidation of VLCFA.

The hypothesis is corroborated with experimental evidence from other researchers that this flux ratio determines the level of oxygen radicals produced. So cell tries to keep the F/N ratio to minimum to avoid dangerous burst of oxygen radicals by leakage of electrons in mitochondria.

So according to this kinetic model, though peroxisomal metabolism of fatty acids is less energy efficient(less ATP yield) than mitochondrial pathway, peroxisomes contribute in dissipating Excess FADH2 arising from VLCFA metabolism.

FADH2 is generated in first step of beta-oxidation. in peroxisomes, FADH2 doesn't go through Electron Transport Chain(Thus less ATP yield!), but rather utilized by catalase for Hydrogen peroxide detoxification.

Monday, November 29, 2010

Post-doctoral position

Postdoctoral Fellow in the Cell Biology of Peroxisomes


to study the molecular mechanisms of peroxisome inheritance in the model organism, Saccharomyces cerevisiae
Link to the Advertisement on Naturejobs.com

in the lab of Prof.Richard Rachubinski,
Department of Cell Biology,
University of Alberta, Canada

See Latest Review by Prof. Rachubinski group
Molecular mechanisms of organelle inheritance: lessons from peroxisomes in yeast
Nature Reviews Molecular Cell Biology, September 2010

Tuesday, October 12, 2010

New insights into peroxisome function and an in vivo peroxisomal trafficking assay

Peroxisomal pipecolate pathway involved in L-lysine catabolism in brain
Therapeutic modulation of cerebral L-lysine metabolism in a mouse model for glutaric aciduria type I.
Sauer et al
Department of General Paediatrics,
Division of Inborn Metabolic Diseases, University Children’s Hospital, Hiedelberg.
Published in journal Brain (A journal of neurology) published online: October 4, 2010
Impact factor of journal BRAIN - 9.49

L-lysine catabolism proceeds via mitochondrial saccharopine pathway or peroxisomal pipecolate pathway. Human L-pipecolate oxidase(PIPOX) is a peroxisomal enzyme carrying C-terminal PTS1 motif (KAHL). Peroxisome Biogenesis Disorder patients lacking peroxisomes or defective in matrix protein import, lack L-pipecolate oxidase activity. Type I Glutaric aciduria patients have genetic defect in glutaryl-CoA dehydrogenase, which leads to accumulation of neurotoxic metabolites. In this paper, Authors used animal model of this disease(gcdh deficient mice) to study the effects of dietary interventions and underlying mechanism of their therapeutic effect. They observed that in brain, Lysine catabolism occurs mainly by peroxisomal L-pipecolate pathway whereas in hepatic cells, it occurs via mitochondrial pathway.

This paper demonstrates that peroxisomes play an important role in brain, by preventing the accumulation of toxic metabolites in L-lysine catabolism. Clofibrate treatment in these mice could further lower the glutaric acid accumulation, which shows that peroxisomal pipecolate pathway could be targeted to recover the defects in mitochondrial enzyme glutaryl-CoA dehydrogenase. Why brain cells prefer action of PIPOX for lysine degradation over saccharopine pathway remains to be better understood.

Peroxisomes as a tool to study motor proteins in cellular traffic
Probing intracellular motor protein activity using an inducible cargo trafficking assay
Kapitein et al.
From the group of Prof. Casper Hoogenraad, Erasmus MC, Rotterdam
Published in Biophysical Journal (Cell Press). Impact Factor - 4.39


Various motor proteins mediate cellular movements on the cytoskeleton network. Kinesins and dyneins are generally involved in long range transport over microtubule network while myosin motors mediate short range movement over actin network. Though the knowledge about how individual motor proteins work was deduced from in vitro studies. In vivo functional dynamics of the motor proteins is still elusive owing to diversity and complexity of the various motor proteins involved in single event. Kapitein et al. report in this paper, an inducible cargo trafficking assay which can be employed in live cells with great control. The assay is based on peroxisomes, so called in vivo peroxisomal trafficking assay. The assay is based on the dimerisation property of two proteins FKBP and FRB on addition of cell permeable rapalog. Rapalogs are non-immunosuppressive analogs of rapamycin which can be used conveniently in ARGENT regulated Heterodimerization Kit produced by Ariad Pharmaceuticals. Pex3 is fused to RFP(for visualisation) and FKBP, whereas the motor protein to be studied is fused to FRB. Both constructs are coexpressed in mammalian cells (in this paper, COS7 cells). Upon addition of rapalog, heterodimeraisation is induced leading to recruitment of desired motor protein to peroxisomes and initiated movement of peroxisomes. Since peroxisomes in COS7 cells are relatively immobile and clustered around nucleus. Authors observed that Kinesins induce +end directed movement of peroxisomes leading to peripheral distribution of peroxisomes. Dyneins result in -end directed movement of peroxisomes towards nucleus. As expected, myosins induce only short range movement.

Authors also did simultaneous visualization of peroxisomes and microtubules and tracked the movements. Peroxisomes where labeled with GFP using Pex26 targeting information, while microtubules were labeled with mcherry. They observed that peroxisomes often pause at microtubule intersections and resume their movement on same or another microtubule after the second microtubule gets depolymerised till the junction.

This in vivo peroxisomal trafficking assay was used by authors in another paper (Kapitein et al, Current Biology, 2010) to demonstrate that kinesins are preferred for trafficking in axons and dyneins are preferred in dendrites in hippocampal neurons. This demonstrates the this assay can be utilized to study individual motor proteins as well as combination of them.

Though this study and the assay were not designed to study peroxisome movement, but to study the properties of motor proteins. But since our knowledge about endogenous movement of peroxisomes and the motor proteins involved is scanty, so I believe that this assay can be directed for peroxisome research also.

Friday, September 24, 2010

Stories behind Nobel

Christian de Duve alongwith Albert claude and George Palade received Nobel prize in physiology or medicine in 1974 "for their discoveries concerning the structural and functional organization of the cell"

de Duve discovered peroxisomes, the organelle which harbors still some more mysteries about its roles and origin. Here is the video of interview with Christian de Duve from Web of stories. Not just one or two videos but whooping 106 videos on the web of stories website.

Its so inspiring to watch him speaking on different topics. I hope every peroxisome researcher will like to listen to it.

a quote from one of the video
"I'm not a genius, I didn't invent relativity, or discover relativity, I didn't discover the double helix, I'm not a colourful personality like Francis Crick or Jim Watson, Richard Feynman and so on. So, I'm just a rather ordinary person with a slightly out of ordinary experience"



de Duve talking about family background



For next videos visit the web of stories website
http://www.webofstories.com/play/15984

Tuesday, September 14, 2010

Update of the week (13-20 September 2010)

New Paper accepted in Hepatology (Impact Factor - 10.84)
Unconjugated bile salts shuttle through hepatocyte peroxisomes for taurine conjugation
Rembacz KP et al
From the group of Klaas Nico Faber

New accepted paper in Journal of Neuroendocrinology (Impact Factor - 3.7)
D-Aspartate Oxidase Localisation in Pituitary and Pineal Glands of the Female Pig
Yamamoto A. et al.
Brief background - DDO (D-aspartate oxidase) is a PTS1 containing peroxisomal protein.

PhD Dissertation by Anca Nenicu
Supervisor - Prof. Dr. Eveline Baumgart-Vogt
Influence of peroxisomes on development, maturation and adult functions of the testis
submitted to Justus-Liebig-Universität Gießen
pdf link
Link posted for academic purposes only.  Please read the associated copyright note on the website

New Paper in PLoS One (Impact Factor - 4.351)
Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer's Disease
Astarita G. et al.
From the group of Prof. Daniele Piomelli
Findings in Brief - peroxisomal D-bifunctional protein activity is reduced in liver leading to impaired DHA biosynthesis in Alzheimer patients.

ABCD1 and ABCD2 are peroxisomal membrane proteins involved in fatty acid transport.
ACOX1 and HSD17B4, are peroxisomal matrix enzymes involved in beta-oxidation functions, both have C-terminal PTS1 signal.

Review in Microbiology Monographs "Structures and Organelles in Pathogenic Protists"
The Glycosome of Trypanosomatids
By Fred R. Opperdoes

Thursday, September 9, 2010

Update of the week (6 September - 13 September 2010)

New Paper in JBC
Conserved and novel functions for Arabidopsis MIA40 in assembly of proteins in mitochondria and peroxisomes
Chris Carrie et al.
From the group of Prof. Jim Whelan
University of Western Australia

New Paper in Journal of Cell Science (JCS, Impact Factor - 6.14)
Koch et al.
From the group of Dr. Cecile Brocard

New Paper in Journal of Inherited Metabolic Disease (Impact Factor 3.6)
An adult onset case of alpha-methyl-acyl-CoA racemase deficiency
Mayo Clinic, USA
Background - AMACR is a peroxisomal protein in humans which contains unusual C-terminal PTS1 (KASL). AMCAR is also localized to mitochondria with N-terminal topogenic signal as characterized by Amery L. et al. Most interestingly AMACR is demonstrated to be Molecular Marker for Prostate Cancer by Jun Luo et al.

New Paper in Biochemical Journal (Impact Factor 5.15)
Ullán RV et al.
From the group of Dr. Juan F. Martín
University of León, Spain

New review in Expert Review of Neurotherapeutics (Impact Factor 2.991)
Phyllis L Faust et al
Columbia University


Poster by Anna Petroni et al. (from 2007 conference)
Metabolism of 8-Iso-PGF2alpha is impaired by CLA in fibroblasts from patients affected by X-ALD
Powerpoint file 
(above links posted for academic purposes only)

Tuesday, August 31, 2010

Update of the week (30 Aug - 5 September 2010)

New Peroxisome articles

New Paper in ENDOCRINOLOGY (Impact Factor - 5.103)
Peroxisomal Localization of the Proopiomelanocortin-Derived Peptides Beta-Lipotropin and Beta-Endorphin
Höftberger R. et al.
Medical University of Vienna, Austria

Rapid Report in New Phytologist (Impact Factor - 6.033)
Myo-inositol abolishes salicylic acid-dependent cell death and pathogen defence responses triggered by peroxisomal hydrogen peroxide
S. Chaouch and G. Noctor
From the Group of Prof. Graham Noctor, Université de Paris sud.

New Clinical method paper in Clinica Chimica Acta (Impact Factor - 2.535)
A rapid and sensitive protocol for prenatal molecular diagnosis of X-linked adrenoleukodystrophy
Fenghua Lan et al.

New Clinical article in Journal of Neurology (Impact Factor - 2.9)
Heterozygous X-linked adrenoleukodystrophy-associated myelopathy mimicking primary progressive multiple sclerosis
Filippo MD et al.

New Research Summary on SciTopics
X-linked adrenoleukodystrophy
Dr Stephan Kemp, Academic Medical Center (AMC), Amsterdam

Clinical Research article in JOURNAL OF CLINICAL ONCOLOGY (Impact Factor - 17.793)
Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor
Katharina Wagner et al.
Hannover Medical School, Germany
Background info- IDH1 is a PTS1 containing protein having dual cytosolic and peroxisomal sub-cellular localisation in humans.

Clinical Trial article in NEUROLOGY
Docosahexaenoic Acid Therapy In Peroxisomal Diseases: Results Of A Double-Blind, Randomized Trial.
Paker MA et al.
From the group of Dr. G.V. Raymond
Kennedy Krieger Institute
Conlcusion of the trial - DHA(Docosahexanoic acid) supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders.

Collection of Peroxisome related clinical articles in NEUROLOGY journal.
http://www.neurology.org/cgi/collection/peroxisomes

Clinical article in Journal of Neurotrauma (Impact Factor - 4.252)
Docosahexaenoic acid prevents white matter damage following spinal cord injury
Rachael Elizabeth Ward et al.

Book Chapter in ASCORBATE-GLUTATHIONE PATHWAY AND STRESS TOLERANCE IN PLANTS
The Peroxisomal Ascorbate–Glutathione Pathway: Molecular Identification and Insights into Its Essential Role Under Environmental Stress Conditions
Sigrun Reumann and Francisco J. Corpas

Friday, August 27, 2010

Update of the week (24-30 august)

New Articles

Novel Peroxin Identified.!
Research Paper in European Journal of Cell Biology (Impact Factor 3.3)
Identification of PEX33, a novel component of the peroxisomal docking complex in the filamentous fungus Neurospora crassa
Managadze D et al
From Ruhr-Universität Bochum

Glycosomal protein identified
Research Paper in Glycobiology (Impact Factor 3.9)
Identification, subcellular localization, biochemical properties and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase.
Mariño K et al.
From the group of Prof. Michael A.J. Ferguson, University of Dundee.

Review in Protoplasma
From signal transduction to autophagy of plant cell organelles: lessons from yeast and mammals and plant-specific features
Sigrun Reumann et al.
Sneak Peek - Comprehensive autophagy review including detailed aspects of Pexophagy, Selective pexophagy in yeast, plants and mammals as well as pexophagy role in pathogenicity.

New Paper in Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Repercussion of a deficiency in mitochondrial ss-oxidation on the carbon flux of short-chain fatty
acids to the peroxisomal ss-oxidation cycle in Aspergillus nidulans.

Magliano P et al.
From the group of Prof. Yves Poirier

New Paper in Molecular Biology of the Cell (MBoC)
Expression of the Salmonella Spp. Virulence Factor SifA in Yeast Alters RHO1 Activity on Peroxisomes
Dani B.N. Vinh et al.
From the Group of Prof.Samuel Miller
University of Washington

Wednesday, August 25, 2010

Artists join hands to help boy with PBD

Max Manciu is seven year old boy and suffering from Peroxisomal Biogenesis Disorder (PBD).
Artist Geary Jones, one of the founders of Destination 1111, has initiated a fundraiser event where artists can showcase and a part of their income will go for Max Manciu's treatment in Spain.

A group of local artists band together tohelp one little boy
News dated - 24 August 2010

Wednesday, August 18, 2010

New subtopic in peroxisome research “Glycosome Research”

Brief intro
Trypanosomes harbor the unique microbody family organelle “Glycosome”, which compartmentalize glycolytic cycle that takes place in cytosol in all other eukaryotes. Glycosomes are essential for trypanosome pathogenicity and hence subjected to research for novel drug targets. Glycosomes being relative of peroxisomes, it will be interesting to keep track of glycosome research.

Pathogens have remarkably different metabolism pathways than higher eukaryotes. For e.g. Plasmodium falciparum, the causative agent for Malaria, does not follow the text-book version of TCA cycle. In fact in recent Nature paper by Olszewski KL et al. “Branched tricarboxylic acid metabolism in Plasmodium falciparum”, authors shown that the TCA cycle of pathogen starts in between at Oxoglutarate and proceeds in two different direction landing on Malate. This means half of the TCA cycle reactions in P.falciparum occur in reverse direction than the known TCA cycle.

Trypansome metabolism holds many more mysteries which are still being uncovered. For e.g the mitochondria of trypanosomes was thought to be metabolically inactive but the proteomics and metabolomics studies are hinting towards active mitochondrial role.

Interestingly some of the pivotal insights in peroxisome linked signalling pathways arose from Glycosomes. For e.g this recent paper in Genes and Development (Impact Factor - 14)
A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway
Balázs Szöőr et al.
From the group of Prof. Keith R. Matthews , University of Edinburg.
“The paper reports the first characterized environmental signaling pathway targeted directly to a peroxisome-like organelle in any eukaryotic cell”

This paper also featured in Editor’s Choice in "Science Signalling" published by AAAS.
Bistable Trypanosome Switch
June 2010

New Glycosome Metabolism paper in JBC
Ablation of succinate production from glucose metabolism in the procyclic trypanosomes induces metabolic switches to the Gly3p/DHAP shuttle and to proline metabolism
Ebikeme C. et al
From the group of Prof. Fréderic Bringaud
CNRS, France

Monday, August 16, 2010

Update of the week (16-22 august)

New Review in "Nature Reviews Molecular Cell Biology" (Impact Factor - 42)
Molecular mechanisms of organelle inheritance: lessons from peroxisomes in yeast
Andrei Fagarasanu, Fred D. Mast, Barbara Knoblach, Richard A. Rachubinski

New biophysical Paper in Biochimie (Impact factor 3.9)
Human liver peroxisomal alanine:Glyoxylate aminotransferase: Different stability under chemical stress of the major allele, the minor allele, and its pathogenic G170R variant

New Clinical Article in Cardiovascular Pathology
Targeted intracellular catalase delivery protects neonatal rat myocytes from hypoxia-reoxygenation and ischemia-reperfusion injury
Authors tested whether SKL-tagget catalase increases the intracellular levels of the antioxidant enzyme catalase in neonatal rat ventricular myocytes and whether catalase-SKL imparts protection against hypoxia–reoxygenation and ischemia reperfusion injury.

Brief intro - in humans, catalase is a PTS1 bearing protein but the PTS1 is quite unique and differs from the consensus SKL. The last four residues of catalase KANL constitute the PTS1 where aspargine and Lysine both are necessary and essential for PTS1 function. catalase PTS1 is not as efficient as other PTS1 signals. Why did cell chose such PTS1, instead of SKL??

There is another recent paper "A Proteome-Wide Perspective on Peroxisome Targeting Signal 1(PTS1)-Pex5p Affinities". The authors experimentally determined the affinity of Pex5 for different PTS1 containing peptides. They observed that Catalse PTS1 has substantially lower affinity towards the pex5 (PTS1 receptor ) than other PTS1 sequences. To account for this disparity, the plausible explanation is the levels of expression, where high affinity PTS1 proteins are less expressed in cell while low affinity PTS1 proteins like catalse are expressed at higher levels.

Tuesday, August 10, 2010

Just Accepted. Hydrogen peroxide breathes life..!

New interesting paper in PNAS (Impact Factor 9.4)

Did you read the title carefully..?
I bet “Not”! So read it again.

How come catalase deletion, high levels of H2O2 lead to increased life span?
For years we have been told that free radicals damage our cells and leads to ageing.
But some recent studies have established at least in some organisms that Oxidative stress is indeed a positive regulator of extended lifespan.
In this paper, authors establish that elevated levels of hydrogen peroxide (either by catalase inactivation or Caloric Restriction) lead to increased lifespan of yeast. These findings are clearly in contrast with the long held theory claiming oxidative stress leads to ageing.
Interesting finding for peroxisome researchers in this paper, is that inactivation of peroxisomal catalase Cta1p results in extended life span which is further extended by caloric restriction.!
H2O2 levels increase as a result of CR or CAT1 deletion. It is assumed that the ROS will damage the cell and the cells should die early. But Authors found that increased lifespan due to increased hydrogen peroxide is by Hormesis effect. Elevated levels of H2O2 induce SOD activity and in turn reduce the levels of superoxide anion. H2O2 is now also established to be secondary messenger for diverse pathways.

Afterthoughts - extension of yeast Chronological lifespan by induction of H2O2 and SOD seems good at cellular level. But how can we be sure about the health of these cells during this extended lifespan. in case of humans, what we seek is extended lifespan but not the one filled with sick health and disabilities.!

Another peroxisome connection -
New Paper in journal "AGING"
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes
Goldberg AA et al.
From the group of Prof.Vladimir Titorenko
The authors observed that pex5Δ mutation leads to shortening of chronological life span (CLS) in Calory Restricted (CR) yeast. (See Figure 1)
The authors used High-throughput chemical genetic screen which led to identification of Lithocholic acid (LCA) as a compound which extends CLS in pex5Δ cells under caloric restriction. The study was further extended to Wild type cells.

Monday, August 9, 2010

Updates (9-15 August 2010)

New Paper in Annals of Neurology (Impact Factor 9.3)
Mutations in PEX10 Are a Cause of Autosomal Recessive Ataxia
Luc Régal et al.
From the group of Prof.Dr.Hans R Waterham

New Paper in Neurogenetics (Impact Factor 3.48)
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes
Matsukawa T. et al
From the group of Prof.Shoji Tsuji

Paper in Kidney and Blood Pressure Research
FPTIII Mitigates Peroxisome-Mediated Oxidative Stress in Kidneys of Spontaneously Hypertensive Diabetic Rats

Review in Clinical Lipidology
Biosynthesis of ether-phospholipids including plasmalogens, peroxisomes and human disease: new insights into an old problem
By Ronald JA Wanders and Pedro Brites

Paper in Iranian Journal of Biotechnology (IJB)
Sorting analysis of mouse peroxisomal protein by in vitro studies  (Pdf format)
Ostadsharif M. et al

New Paper in Chemistry & Biodiversity (Impact Factor 1.9)
Comparative Characterization of Three d-Aspartate Oxidases and One d-Amino Acid Oxidase from Caenorhabditis elegans (Pdf)
Katane M. et al.
Background info - DAO and DDO1 are peroxisomal PTS1 containing proteins. D-Amino acid oxidase is reported to be associated with Schizophrenia (Molecular Psychiatry, 2008) and Familial amyotrophic lateral sclerosis (PNAS, 2010)

Tuesday, August 3, 2010

Updates (1-8 August 2010)

New Paper in Experimental Cell Research (Impact Factor 3.58)
Dynamin-like protein 1 at the Golgi complex: A novel component of the sorting/targeting machinery en route to the plasma membrane
Bonekamp NA et al.
From the group of Prof.M Schrader, Aveiro, Portugal
Sneak Peek - Eukaryotic cell typically contains several single and double membrane bound organelles. To maintain them, cell utilizes specific as well as shared components. Dynamin like proteins like Dnm1, DLP1/Drp1 are involved in membrane dynamics at mitochondria and peroxisomes. the role of Dnm proteins in peroxisome division was recently uncovered. Interesting insights in organelle biology are pouring in these-days which includes the paper on retromer complex (Vps35, Vps26) involvement in mitochondria derived vesicles transport to peroxisomes. There were controversial reports on cellular localisation of DLP1/Drp1 in different cell lines. In this paper, authors dissected the golgi localised DLP1/Drp1 and find a novel function for them beyond the known repertoire of functions at mitochondria and peroxisomes.

There is also one interesting paper recently "A Mutation in the Mitochondrial Fission Gene Dnm1l Leads to Cardiomyopathy" in PLoS Genetics (impact factor ). In this paper authors identify the gene responible for inherited dilated cardiomyopathy (DCM) using heterozygous mouse fibroblasts (Since homozygous mutants die before birth).
Fig.4D from the PLoS Genetics paper
"peroxisomal morphology is altered by the Python mutation"

__________________________________________________________________

New Peroxisome Paper in PLoS ONE
Genome-Wide Analysis of Effectors of Peroxisome Biogenesis
Saleem RA et al
Institute for Systems Biology,
Seattle, Washington, United States of America.

Figure 3. from the paper
Vps52p, Pir3p and YKL015C are novel peroxisome inheritance factors.

__________________________________________________________________

High Impact peroxisome paper in PNAS (impact factor 9.4)
Different functions of the C3HC4 zinc RING finger peroxins PEX10, PEX2, and PEX12 in peroxisome formation and matrix protein import
Jakob Prestelea et al
From the Group of Prof. Dr. Christine Gietl
Technische Universität München
Germany
___________________________________________________________________

High impact Clinical Peroxisome paper in American Journal of Human Genetics (Impact Factor 12.3)
Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome.
Pierce SB et al
From the group of Professor Mary-Claire King,
Department of Genome Sciences, University of Washington

Prof.Mary-Claire King is the famous scientist who had identified BRCA1 (breast cancer type 1 susceptibility protein), the human tumour suppressor gene in 1990 at UC Berkeley.
In another pioneering achievement, in this paper Prof. King group report the identification of  the genetic basis for Perrault syndrome (also known as XX gonadal dysgenesis) for the first time. Surprisingly the single gene D-bifunctional protein (DBP) coding for the peroxisomal multi-functional enzyme was found to be mutated leading to reduction in the transcript levels.

Thursday, July 29, 2010

Peroxisome Posters in Yeast Meet 2010

Yeast Genetics and Molecular Biology Meeting 2010
Date - July 27 – August 1, 2010
Place - University of British Columbia, Vancouver, Canada.

Program and Abstract Book
http://www.yeast-meet.org/2010/pdf/book.pdf#pagemode=bookmarks

NOTE - The abstract hyperlinks are not properly landing on the abstract page, though I update them everyday with working links. Inconvenience Regretted

Poster Sessions
Cell Biology: Mitochrondria/Vacuoles/Peroxisomes
(I am mentioning only Presenting author under the abstract title, for full author list and abstract visit the Conference website)

28 July 2010 (Wednesday)
101A
Genome-wide analyses of the function of Pex11, a protein involved in processes beyond peroxisome proliferation.
Uros Petrovic

466A
Integrated Phosphoproteomic Analysis of a Signaling Network Governing Nutrient Response and Peroxisome Induction.
Ramsey Saleem

481A
A new fluorescent probe to assess intra-cellular and intra-organellar redox states.
Masahide Oku

97B
Interrogation of Integral Membrane Protein Complexes in Peroxisome Biogenesis.
Arvind Jamakhandi

217B
Novel anti-aging compounds extend yeast life span by targeting a programmed necrotic cell death pathway.
Vladimir Titorenko

29 July 2010 (Thursday)
103C
The role of Pex11 family members in peroxisome proliferation in Hansenula polymorpha.
Ruchi Saraya

30 July 2010 (Friday)
574D
Metabolic Engineering of Yarrowia lipolytica: Production of Eicosapentaenoic Acid-Rich Oil for Commercialization.
Zhixiong Xue

105E
Oxidative stress resistance and peroxisomal proliferation in lager fermentation.
Natalia Solodovnikova

Wednesday, July 28, 2010

New Peroxisome Articles (Update 21-28 July 2010 )

Pex11pβ-mediated growth and division of mammalian peroxisomes follows a maturation pathway
JCS Online accepted article
Delille HK et al
Prof. Michael Schrader Group

(From the Note in above paper, Paper not yet online on JCS)
PEX11-family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance
JCS in press article
Koch et al.
Prof. Cecile Brocard and coworkers

Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene
Journal of Medical Genetics (Impact Factor 5.75)
Ebberink MS et al
Dr. Sacha Ferdinandusse, University of Amsterdam

Targeting of Pex8p to the peroxisomal importomer
European Journal of Cell Biology (Impact Factor 3.3)
Deckers M et al
Prof. Ralf Erdmann Group

De novo synthesis of peroxisomes upon mitochondrial targeting of Pex3p
European Journal of Cell Biology (Impact Factor 3.3)
Rucktäschel R et al
Prof. Ralf Erdmann Group

Review
Protein Import Machineries of Peroxisomes
Biochimica et Biophysica Acta (BBA) - Biomembranes (Impact Factor 3.9)
Rucktäschel R et al.
Prof. Ralf Erdmann Group

Clinical, Biochemical and Molecular Characterization of Peroxisomal Diseases in Arabs
Clinical Genetics (Impact Factor 3.3)
Shaheen R et al
Dr. Fowzan Alkuraya Group
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Catabolite repression of Aox in Pichia pastoris is Dependent on Hexose Transporter PpHxt1 and Pexophagy
Applied and Environmental Microbiology (Impact Factor 3.8)
Zhang P et al
Prof. Xiangshan Zhou, East China University of Science and Technology

The Arabidopsis peroxisomal ABC transporter, comatose, complements the Saccharomyces cerevisiae pxa1 pxa2Δ mutant for metabolism of long chain fatty acids and exhibits fatty acyl-coa stimulated atpase activity
JBC
Nyathi Y et al
Prof. Alison Baker Group

A proteomic approach towards the identification of the matrix protein content of the two types of microbodies in Neurospora crassa
Managadze D et al
Proteomics (Impact Factor 4.58)
Dr. Hanspeter Rottensteiner, Ruhr-University Bochum

Saturday, July 17, 2010

Obsoletely Correct..My Toilet Philosophy applied to Peroxisomes

Hello Peroxisome Blog Readers,

I have a blog on Nature Blogs titled "GeeK of Science"
In a series of posts, I am trying to generate philosophy about science from day to day activities.

This time it is Toilet Philosophy.
In new post "Obsoletely Correct" I tried to apply this new term on small scale to peroxisomes..
I hope you will find the blog article Very Funny yet Insightful...

Wednesday, July 14, 2010

Updates of the week 12-18 July 2010

New Peroxisome Papers

Niche - High-Throughput screening
Journal - International Journal of High Throughput Screening
North Carolina Central University
Fig.1 from the paper..



Niche - Three Minireviews in the FEBS Journal.
MINIREVIEW SERIES - Peroxisomes as dynamic organelles
Introduction to review series by Prof. Ida J. van der Klei

Peroxisomes as dynamic organelles: autophagic degradation
Masahide Oku et al.
From the group of Prof. Yasuyoshi Sakai,
Kyoto University, Japan

Peroxisomes as dynamic organelles: peroxisome abundance in yeast
Ruchi Saraya et al.
From the group of Prof. Ida J. van der Klei
University of Groningen, Netherlands

Peroxisomes as dynamic organelles: peroxisomal matrix protein import
Janina Wolf et al.
From the group of Prof. Ralf Erdmann
Ruhr-Universität Bochum, Germany

Niche - Review
Peroxin 5: a cycling receptor for protein translocation into peroxisomes
Chris P. Williams, Will Stanley
Journal - The International Journal of Biochemistry & Cell Biology

Niche - Case report
Refsum’s Disease – Use of the Intestinal Lipase Inhibitor, Orlistat as a Novel Therapeutic Approach to a Complex Disorder
Journal - Journal of Obesity
Provisional PDF from the publisher - Link 
Nimalie Perera et al.
From the group of Prof. David R. Sullivan
Authors report the results of novel therapy on Refsum disease patients with intestinal lipase inhibitor orlistat. Authors observed significant reduction in phytanic acid levels and retardation of dermatological and neurological symptoms.

Niche - Cell signalling
Spermidine Oxidase-derived H2O2 Regulates Pollen Plasma Membrane Hyperpolarization-activated Ca2+-permeable Channels and Pollen Tube Growth
Journal - The Plant Journal
Juyou Wu et al.
From the group of Prof. Shaoling Zhang
Nanjing Agricultural University, China
Authors identified that Arabidopsis peroxisomal polyamine oxidases (PAO) oxidize spermidine to release H2O2 which acts as messenger for inducing the opening of Ca2+-permeable channels. This event is critical for pollen tube growth.
(on larger note, this paper hints towards peroxisome as source for critical cellular signal transduction events like mitochondria.)

(This simplified diagrammatic representation of the results from above paper is made by me using www.proteinlounge.com.)



Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of group VIB Ca2+-indpendent phospholipase A2 (iPLA2γ) deficient mice
Journal - Journal of Lipid Research
Emiko Yoda et al.
From the group of Prof. Shuntaro Hara
iPLA2γ (Group VIB Ca2+-independent phospholipase A2) has dual mitochondrial (N-terminal) as well as peroxisomal localization signals (C-terminal SKL). (Ref.)

Niche - From EBEC Abstract book
Biochimica et Biophysica Acta (BBA) - Bioenergetics
Peroxisomal transporters associated with β-oxidation
Theodoulou et al.

Tuesday, July 13, 2010

Peroxisome Puzzles..

Gene. 2010 Jan 15;450(1-2):18-24.
Duhita N et al (Japan)

Gene. 2010 Jun 25. [Epub ahead of print]
Gabaldón T et al (Spain)

Phylogenetic analysis of Pex1/6 proteins was used as basis for determining the relatedness of these peroxins to actinobacterial or ER proteins and to determine the evolutionary ancestor of peroxisomes.
At least one of the paper has to be wrong. or there is third possibility that phylogenetic analysis of Pex1/6 itself is insufficient criteria to determine the origin of peroxisomes.!

Friday, July 9, 2010

Before Pubmed..!





New High Impact Peroxisome Paper in Current Biology (Cell Press) (2009 Impact Factor - 10.992)

Vps35 Mediates Vesicle Transport between the Mitochondria and Peroxisomes
Emélie Braschi et al.
Prof.Dr.Heidi M. McBride.
University of Ottawa Heart Institute, Canada.
Lab webpage

McBride group had previously shown that Mitochondria derived vesicles(MDV) can carry specific cargos to peroxisomes.
Cargo-Selected Transport from the Mitochondria to Peroxisomes Is Mediated by Vesicular Carriers
Neuspiel et al, Current Biology, 2008

In the recent stunning findings, McBride group reports that MDV transport between mitochondria and peroxisomes requires Vps35 and Vps26a, the components of Retromer complex which is required for endosome to golgi complex transport.

"Does Peroxisome turn Midwife??"

Fis1, Dnm1, MAVS, maybe prohibitins... the list of mitochondrial proteins having roles in peroxisome function is increasing.

There is another new paper accepted in MCB (Impact factor 5.9) 

This paper establishes Hep27 as authentic mitochondrial protein but also somehow localized to nucleus. Interestingly, Hep27 has a putative PTS1 (TRL) and hence also predicted to be peroxisomal (Ref.). This type of targeting signal architecture does indeed regulate spatio-temporal distribution of proteins, since a protein with both N-terminal MTS and C-terminal PTS1 will get sorted to mitochondria first and since mature form lacks MTS the PTS1 can function for further peroxisomal sorting

Authors of the above MCB paper speculate whether mature mitochondrial Hep27 is transported to nucleus via peroxisomes by Mitochondria Derived Vesicles (see MDV-peroxisome paper in Current Biology).
If confirmed, this novel route of "Mitochondria --> Peroxisomes--> ER? --> Nucleus" might uncover unanticipated complexities than ever expected!!
since Hep27 is interacting with C-Myb (Proto-oncogene), Mdm2 and stabilizing p53, it will be under intense investigation in future.

Identification of Mitochondrial-derived Vesicles


P Rippstein,M Neuspiel,A Schauss,V Soubannier,E Braschi and HM McBride (2010).

Thursday, July 8, 2010

All yeasts are not equal.. The chromatin regulation differs for peroxisome genes.

Recent paper from PLoS Biology
The Role of Nucleosome Positioning in the Evolution of Gene Regulation
Tsankov AM, Thompson DA, Socha A, Regev A, Rando OJ (2010)
PLoS Biol 8(7): e1000414. doi:10.1371/journal.pbio.1000414

Following is the reproduction of peroxisome specific data and figures from the above paper.
The data is reproduced here for academic purposes of researchers interested in peroxisome research. 
The blog readers are thankful to PLoS publishers for providing the free access to the articles.

Peroxisome genes are highly expressed in D. hansenii, C. albicans, and Y. lipolytica, where they are packaged with long (but not deep) NFRs, despite no enrichment for Poly(dA:dT) tracts.


Changes in GRFs Contribute to Chromatin Divergence Between Species in Peroxisomal Genes
In some cases, the gain or loss of binding sites for GRFs can contribute to divergence in chromatin organization, coupled to phenotypic changes. Most notably, peroxisomal genes are associated with wider NFRs in Y. lipolytica, C. albicans, and D. hansenii, and shorter NFRs in subsequently divergent species (Figures 3E and S15F), but are not associated with intrinsic anti-nucleosomal poly(dA:dT) tracts in any of the 12 species. Instead, we find that these genes' promoters are enriched for PolyG and Rsc3/30-like sites in Y. lipolytica, C. albicans, and D. hansenii, but not in other species. This suggests an evolutionary scenario where either a Rsc-like motif or PolyG-based nucleosome depletion was the ancestral mechanism controlling peroxisomal genes, and was subsequently lost in the LCA of the clade spanning S. kluyverii and S. cerevisiae. This scenario is consistent with the higher expression of peroxisomal genes in Y. lipolytica (where peroxisomes are particularly central for carbon metabolism) and C. albicans (where peroxisomes play a key role in virulence).



(Note - I tried to understand the chromatin biology of peroxisome genes, but i need to read more about basic concepts. So I will come up with detailed article about this paper later..)

Tuesday, July 6, 2010

Future Event - 2010 SSIEM Annual Symposium

Society for the Study of Inborn Errors of Metabolism (SSIEM)
31st August - 3rd September 2010
Istanbul

Peroxisome related talks on 1st September 2010 (Wednesday)

11:00 – 11:15
New insights into quarternary structure of PEX26 point to potential alternative functions of this peroxin
A.S. Lotz, Germany

Plenary Session IV
16:30–17:00 -
Peroxisomal Disorders of Bile Acid Metabolism
Sacha Ferdinandusse, Amsterdam, The Netherlands

Monday, July 5, 2010

Peroxisome Abstracts from Future..

SEB Annual Main Meeting 2010
Clarion Congress Hotel, Prague, Czech Republic
30th June - 3rd July 2010

Peroxisome related abstracts in poster session

From the session - Plant Cell Biology: Cell Biology of Plant Defense http://www.sebiology.org/meetings/Prague/Abstracts/C5.pdf

Poster Session 1st July 2010 (Thursday) 17:00 – 19:00

C5.38 
Cross-kingdom characterization of peroxisomal ABC transporters
Xuebin Zhang (Rothamsted Research) et al. 
The authors have performed heterologous expression of mammalian ABC transporter proteins adrenoleukodystrophy protein (ALDP), ALD related protein, PMP70 and P70R which are properly sorted to peroxisomes(ALDP,ALDRP,PMP70) and ER(P70R) in plants(tobacco epidermis cells). They observed that Arabidopsis Pex19_1 can interact with both plant as well as human ABC proteins. The major observation by the authors is that disease causing mutant human ALDP proteins which are either degraded or mislocalized in human cells, are still properly targeted to peroxisomes in plants upon heterologous expression and are stable. 

C5.43
Novel chemical inhibitors provide fresh insights into peroxisome form and function 
Laura-Anne Brown (University of Leeds) et al. 
Different yet elegant approach is being used by Dr. Alison Baker group to gain better understanding of peroxisome biogenesis in plants. To overcome the limitations of lethality or redundancy in classical genetics approach, the authors are using chemical genetics approach to screen small molecule compounds which perturb peroxisome biogenesis by mislocalizing peroxisome directed GFP reporter. The authors have come up with two compounds, one being potent inhibitor of peroxisomal protein import while other inhibits peroxisomal β-oxidation. 

C5.44 
Dissecting the peroxisomal protein import pathway using novel small molecule probes 
Catherine O’Leary-Steele (University of Leeds) et al. 
Authors present the data about the chemical genetic screen for the compounds disturbing peroxisomal protein import in plants. Authors identified three small molecule inhibitors of peroxisomal import affecting both PTS1 as well as PTS2 proteins. Authors are optimizing these lead compounds to reduce the cytotoxicity, and finding the binding partners using surface Plasmon Resonance analysis. The efforts are also going to identify the interactors (peroxisome membrane fraction proteins) by pull down experiments and proteomics.

Saturday, June 26, 2010

Notable Peroxisome articles of the week

This is the list of most recent peroxisome related articles accepted in different journals last week.
  1. Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytes
    Journal - Glia (Impact Factor - 5.6)
    Authors - Astrid Bottelbergs et al. (Myriam Baes Group)
    Brief Description - Studies on neuronal cells from Pex5 knockout mice

  2. Peroxisomes in zebrafish: distribution pattern and knockdown studies
    Journal - Histochemistry and Cell Biology (Impact Factor - 2.32)
    Authors - Krysko O et al. (Myriam Baes Group)

  3. Identification of a substrate-binding site in a peroxisomal β-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative
    Journal - JBC (Impact Factor - 5.3)
    Authors - Kashiwayama Y et el. (Tsuneo Imanaka Group)

  4. A Mutation in the Mitochondrial Fission Gene Dnm1l Leads to Cardiomyopathy
    Journal - PLoS Genetics (Impact Factor - 9.5)
    Authors - Ashrafia H. et al (T. Neil Dear group, Leeds, UK)
    Brief Description - Python (Dnm1l, Dynamin 1 like protein) mutation directly involved in morphological impairment of mitochondria and peroxisomes, leading to heart disease (dilated cardiomyopathy)

Friday, June 25, 2010

Role of Peroxisomes in Dengue response

The recent paper in PLoS NTD caught my attention since Pex14 and Pex13 are reported to be among 273 “Common Dengue Response genes” which are up-regulated in Dengue virus infections. So I thought of having a closer look into the microarray data and I fished out peroxisomal genes that are up or down-regulated in Dengue infection.

Citation -
Loke P, Hammond SN, Leung JM, Kim CC, Batra S, et al. (2010)
PLoS Negl Trop Dis 4(6): e710. doi:10.1371/journal.pntd.0000710

(Kindly note that authors report vast microarray data, but I am discussing only about peroxisome specific genes in this post. Please consult the original paper for other details and proper context)


Dengue Virus (DENV) is single stranded RNA virus transmitted to human by mosquito Aedes aegypti. Dengue viral infection elicits wide spectrum of clinical manifestations. The authors performed transcriptional profiling of patient samples and found that there is distinct transcriptional profile associated with each clinical outcome.

*  DF    - Dengue Fever
*  DHF - Dengue Hemorrhagic Fever
*  DSS  - Dengue Shock Syndrome

Peroxins/Peroxisomal proteins significantly up/down regulated in Dengue infections

It should be noted that Pxmp2, the peroxisomal integral membrane protein is up-regulated in all Dengue clinical outcomes. So I will discuss about Pxmp2 in detail.

Confusion between PMP22 and Pxmp2

Pxmp2 is a peroxisomal multipass integral membrane protein which is highly expressed in tissues like liver, heart and kidney. Another peroxisomal membrane protein PMP70 is now known as Pxmp1. Since size of Pxmp2 is 22kD, it was also known as PMP22. But currently, PMP22 is official name of Peripheral Myelin Protein which is totally unrelated to Pxmp2.

Pxmp2 carries two distinct peroxisomal targeting signals, one in each N-terminal and C-terminal domain, both of which interact with Pex19 and get sorted to peroxisome membrane. Pxmp2 is the first peroxisomal protein experimentally shown to be a channel forming protein by Hiltunen group (Rokka et al). It is speculated by the authors that since Pxmp2 channel is open for longer times, it might allow non-specific small molecule transport.

Figure 1 from the paper of Rokka et al. (Compare the electron density between two)

Friday, June 18, 2010

Crispy Hot Peroxisome Papers.. Fresh from the oven of science.

Peroxisomes in zebrafish: distribution pattern and knockdown studies

Histochem Cell Biol. 2010 Jun 17. [Epub ahead of print]
by the group of M. Baes at Katholieke Universiteit Leuven, Belgium

Abstract - (from Pubmed)
          Peroxisomes are organelles that are essential for normal development in men and mice. In order to explore whether zebrafish could be used as a model system to study the role of peroxisomes, we examined their distribution pattern in developing and adult zebrafish and we tested different approaches to eliminate them during the first days after fertilization. In 4-day-old embryos, catalase-containing peroxisomes were obvious in the liver, the pronephric duct and the wall of the yolk sac, but transcripts for peroxisomal matrix and membrane proteins were also detected in the head region from 24 h post-fertilization. In adult zebrafish, catalase-containing peroxisomes remained prominent in the hepatocytes, the renal proximal tubules and the intestinal epithelium. Several peroxins, essential proteins for the biogenesis of peroxisomes, were targeted using knockdown approaches. Two morpholinos, blocking, respectively, splice sites in pex3 and pex13, only induced a short in frame deletion or insertion in the transcripts and did not result in the elimination of peroxisomes after injection into one-cell embryos. A morpholino blocking translation of pex13 was able to reduce the number of peroxisomes to variable extents. Finally, overexpression of a potential dominant negative fragment of Pex3p did not result in deletion of peroxisomes from developing zebrafish. 
We conclude that in zebrafish 
(1) peroxisomes, as visualized by DAB cytochemistry for catalase activity, are most conspicuous in the liver and renal tubular epithelium; this pattern is reminiscent of peroxisome occurrence in mammalian organs
(2) our approaches to eliminate these organelles during development by targeting peroxins were not successful.



New Review accepted in Journal of Lipid Research (JLR)
Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism
Paul P. Van Veldhoven
K.U.Leuven, Belgium