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.

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.

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

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.