Friday, May 28, 2010

Peroxisome-Lipid bodies Romance

(Note - Lipid bodies are also known as Lipid Droplets LDs )
     
Peroxisomes interact with various organelles like ER, mitochondria, chloroplast which involves proteins as well as various metabolite transport. Lipid bodies are intracellular cytoplasmic triacylglycerol storage sites in cells like adipocytes. Recently much insight has been gained into protein components of lipid droplets and interaction of LDs with other organelles, especially with peroxisomes. Peroxisomes and mitochondria are involved in fatty acid beta oxidation so naturally, the lipids are mobilized from LDs and further metabolized in other organelles as energy source.

Many viruses are known to use distinct organelles as a site for their localization and replicative proliferation. For e.g. Hepatitis C virus on lipid bodies (McLauchlan J, 2009) and Tomato bushy stunt virus (TBSV) on peroxisome membrane in plants (McCartney AW et al., 2005). Indeed many viruses employ the strategy where viral genome encodes pathogenicity factors with targeting signals for the host organelle. This is hot topic thesedays due to availability of viral genomes as well as understanding of organelle targeting signals.(See the related event at end of the post).
         
A new paper has been accepted in The Plant Journal (2008 Impact Factor - 6.493, Source - Journal Homepage) titled “The AtCPK1 Calcium-dependent Protein Kinase mediates pathogen resistance in Arabidopsis. (Click here to see abstract)
"Accepted Article" , The Plant Journal , Online published - 18 May 2010

Lipid bodies perform crucial roles in plants, most interestingly in Seeds where energy stored in form of lipids is utilized during germination. Since much is known about LDs in mammals due to their importance in cardiovascular diseases, Plant LD remain relatively less explored. In this paper authors have unraveled a protein in Arabidopsis which is dually localized on lipid bodies and peroxisomes. Calcium-dependent Protein Kinase from Arabidopsis thaliana (AtCPK) was analyzed. AtCPK1 is shown to be involved in innate immunity of plants against various pathogens. Authors have also deduced that the pathway involved in CPK mediated immunity is Salicylic Acid (SA) dependent signalling pathway leading to expression of disease resistance genes.

In recent "Cell" paper by it was shown that Peroxisomes play important role in innate immunity against Viral infections through dually localized protein MAVS on mitochondria and peroxisomes (Dixit et al, 2010). Peroxisome localized MAVS elicits Interferon independent gene response and impart immediate but short term protection and mitochondrial MAVS giving delayed but longer INF-dependant gene expression response. Thus complementing activities of the two organelles is necessary for sustained immune response (Dixit et al, 2010).
Similarly in plants, AtCPK1 is shown to be localized to both organelles Lipid bodies and peroxisome and are involved in plant immune response against pathogens which involves Salicylic acid signalling pathway as demonstrated by authors in this paper.

The peroxisomes now gain centre stage as a functional entity involved in not mere free radical detoxification or fatty acid metabolism but in life saving Immune responses. In both cases of plants and humans, the actual cascade of immune response originating from peroxisomal part remains to be deduced in future studies
  
Related Event -
Talk by Prof. Dr. Sigrun Reumann
“Identification of peroxisome-targeted pathogen defense proteins by new subcellular targeting prediction algorithms”
Details - Click Here

(Note - All peroxisome related events can be found under “Events Tab” on this blog, customized in a calendar. But I will also post the events related to the specific topic in the blogpost itself.) 

Tuesday, May 25, 2010

Updates of the week

Genome wide gene deletion library of S.cereviseae has greatly facilitated the better understanding of various aspects of eukaryotic biology. Fission yeast, S.pombe quiet differs from Budding yeast  in various metabolic and structural aspects. The recent paper by Dong-Uk Kim et al, in Nature Biotechnology, report the construction and analysis of comprehensive heterozygous diploid deletion mutants.
Overwhelmingly 98.4% of the S.pombe genome was covered and analysed.

Nature Biotechnology (2010), Published online16 May 2010

This collection can now complement and assist further insight into peroxisome biogeneis and metabolism dynamics coupled with S.cereviseae gene deletion library.
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The Latest issue of Biochem. Soc. Transac. Features 'Organelle Biogenesis and Positioning in Plants'.
Peroxisomes. mitochondria.. Plastid.. Nucleus… The issue is full of interesting articles.. There is so much to read!!
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7th FENS Forum of European Neuroscience
Amsterdam, RAI Convention Centre
Federation of European Neuroscience Societies (FENS)
July 3-7, 2010

Two peroxisome related Posters will be presented in this event

Fanelli F. et al.
The authors report their finding on peroxisomal involvement in nervous tissues in Transgenic mouse model for Alzheimer disease.

Kunze M. et al
Authors report the identification of first brain specific peroxisomal matrix protein. Brain specific splice form of the potassium channel interacting protein 4 (KvChIP4) is a novel PTS2 protein and EFGP fusion protein is peroxisomal.
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6-10 June 2010, Pacifio Yokohoma, Japan

Poster - Farmer LM et al, (from group of Prof. Bonnie Bartel)

"The lon2 protease contributes to continued matrix protein import into peroxisomes"

The authors mention in abstract that they are using forward genetic screen for lon2 suppressors to identify potential lon2 targets and/or regulators combined with biochemical approach. Lon2, is an AAA-Atpase/protease which itself is not directly involved in PTS2 processing but mutant shows accumulation of unprocessed PTS2 proteins.

Friday, May 14, 2010

Outsourcing Biogenesis

Role of ER in peroxisome biogenesis in native conditions in wild type cells is quiet debated. Several reports on mitochondrial proteins residing also on peroxisomes are emerging thesedays. Most recent entry in this list of dually localized proteins is MAVS (Mitochondrial Antiviral Signaling protein) which plays critical role in antiviral response (Dixit et al, Cell, 2010). Pex19 dependant targeting of mitochondrial tail anchored proteins to peroxisomal membrane is confirmed in case of Fis1 (Dellile et al, JBC, 2008), Vps1 (Vizeacoumar, JBC, 2006) and partial dependancy of  Dlp1 on Pex11 for peroxisomal targeting is also reported (Li et al, JBC, 2003). Vescicular carrier mediated transport of specific cargo from mitochondria to peroxisome is also reported (Neuspiel et al, Curr. Biol, 2008).

This indeed stresses the existence of wider range of inter-organellar communication between mitochondria and peroxisomes. Especially this cooperation can be at peak level in specialized cells like photocytes, the light emitting cells from fireflies. Bioluminescence in fireflies involves ATP dependant activation of Luciferin by Luciferase and its subsequent release of energy in form of light pulses. Both luciferase and luciferin are localized in peroxisomes whereas mitochondria provide ATP and regulate the oxygen supply in tracheal system surrounding photocytes. (More Info.) Complexity is more in case of plant cells where there is cross talk between chloroplast, mitochondria and peroxisomes.

Similar to peroxisomes, the biogenesis of autophagosomes is in controversy whether they are formed de novo or from pre-existing membranes. In case of yeast, autophagosomes are generated from PreAutophagosomal Structures (PAS) formed of ATG proteins near vacuaole. Whereas there was much ambiguity in knowledge about this process in mammalian system.  
                   Recent paper in Cell by Hailey et al titled “Mitochondria Supply Membranes for Autophagosome Biogenesis during Starvation” trace the autophagosomal membrane origin to mithochondria in mammalian cells (at least during starvation!). Though autophagosomal membrane can be formed from ER or plasma membrane depending upon the kind of stress. In this paper, authors offer a conclusive proof that autophagosome formation in starvation induced autophagy relies on mitochondria for the lipid components. Intriguingly only lipid components from mitochondrial outer membrane and not the mitochondrial proteins are utilized for autophagosome biogenesis. The authors present elegant experimental proofs that mitochondria-autophagosome interaction is an entirely independent and native phenomenon other than mitophagy itself.

The ability of mitochondria to provide membrane template for biogenesis of vescicles and autophagosomes reminds the peroxisome biologists that in the debate of ER-Peroxisomes, we should not miss mitochondrial role in between.


-Vishal Kalel. -

Thursday, May 13, 2010

JBC accepts three papers on structures of peroxisomal enzymes

Running Title - Redox control of peroxisomal thiolase
Valerie Pye et al
• Crystal structures of KAT from Arabidopsis thaliana and Helianthus annuus solved to 1.5 Å and 1.8 Å resolution
• The Arabidopsis KAT is a peroxisomal protein carrying N-terminal Type 2 Peroxisomal Targeting Signal (PTS2) RQX5HL
• Since PTS2 and adjacent residues form disordered structures, Authors have solved the structure for 36-462 residues of KAT

Running Title - Structure of Multi-functional Protein, MFP2
Susan Arent et al
• MFP2 is 725 amino acids protein with C-terminal Peroxisomal Targeting Signal (PTS1) with sequence SRL
• The structure of the full-length AtMFP2 reported in this paper is the first structure of a full-length peroxisomal MFP
• Resolution of crystal structure: 2.50 Å

Prasad Kasaragod et al
Running Title - The crystal structure of rat peroxisomal MFE1
• MFE1 is 727 amino acids protein with C-terminal PTS1 sequence SKL
• Crystal structure of CoA liganded full length Rat Peroxisomal type 1 MultiFunctional Enzyme solved at 2.8Å resolution.

Tuesday, May 11, 2010

Phd Research position at INSERM, France.

Phd Research position
at The Department of Nutrition
Inserm U866, Université de Bourgogne, France

Project description in brief -
To characterize the regulation and the physiological role of an L-carnitine dependent enzyme that is present in the peroxisome and involved in VLCFA metabolism: the Carnitine octanoyl transferase (COT).


For details Visit the link - PhD Position, INSERM

Saturday, May 8, 2010

Peroxisome Papers of April 2010

April 2010 

A yeast MAPK cascade regulates pexophagy but not other autophagy pathways.
Journal - JCB
Tags - Pexophagy, MAPK, breakthrough

Integrated Phosphoproteomic Analysis of a Signaling Network Governing Nutrient Response and Peroxisome Induction
Journal - MCP
Tags - Proteomics, global, yeast peroxisomes

Lipid Rafts are Essential for Peroxisome Biogenesis in HepG2 cells
Journal - Hepatology
Tag - Lipid rafts in Peroxisome, micro-domains in peroxisome membrane

Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase
Journal - PNAS
Tag - Peroxisome and disease, DAO, D-amino acid oxidase

Visual Follow-Up in Peroxisomal-Disorder Patients Treated with Docosahexaenoic Acid Ethyl Ester
Journal - Investigative Ophthalmology & Visual Science
Tags - Treatment, peroxisomal disorder

The light of the firefly under the influence of ethyl acetate
Journal - J. Biosci.
Tag - Less known functions of peroxisome, Light, luciferase, luciferin
Idea - Can Luminescence of Luciferase be used as quantitative indicator of peroxisome number or content?

Friday, May 7, 2010

ECFG10 peroxisome related abstracts



Leiden, Amsterdam, Netherlands 
29 MARCH - 1 APRIL 2010 

Peroxisome related abstracts from the conference

1. Biogenesis and evolution of the fungal Woronin body
      Gregory Jedd
2. The role of microbodies in penicillin production
       L. Gidijala….Iaa J. van der Klei
3. Control of organelle differentiation and copy number by positive feedback to import competence
       F. Liu….Gregory Jedd
4. Penicillium chrysogenum Pex14/17p: a novel component of the peroxisomal membrane that is important for penicillin production 
      L. Opalinski….Ida J. van der Klei
5. Novel peroxin, Fam1p of Colletotrichum orbiculare is essential for pathogenesis and associates with Woronin bodies
      Y. Kubo….Richard O’Connell

Tuesday, May 4, 2010

Peroxisomal Pore in news

"The peroxisomal importomer constitutes a large and highly dynamic pore".
The paper from our lab is in news


Research Highlight in Nature Reviews Molecular Cell Biology
 
Highlights in Nature Structural & Molecular Biology
Chief Editor of Nature Structural & Molecular Biology Arianne Heinrichs discusses this pore paper in brief.

Faculty of 1000 biology reviews the Pore paper
and the F1000 Factor for this paper is whooping 6.6 and recommended as "Must Read"

Monday, May 3, 2010

Unconventional protein secretion

               Soluble proteins destined for secretion contain N-terminal or internal signal peptide and they enter co- or post translationally into ER lumen, ultimately travelling trough golgi to plasma membrane. Interestingly many proteins like Fibroblast growth factor 2 (FCF-2), cytokine IL-1β are secreted independent of ER-golgi route. There are many pathways by which this feat can be achieved. The recently discovered pathway for secretion of Acb1 is surprising since it involves peroxisomal components.
                Two articles in JCB shed light upon unconventional secretion of protein Acb1 (acyl CoA-binding protein). First article by Duran et al. explores the participation of autophagosome mediated exocytosis whereas second article by Manjithaya et al. establishes the critical role of peroxisomal components in this process.
                Pex11 is essential for transport of MCFA to peroxisomes. Faa2 is a PTS1 containing acyl-CoA synthetase which is transported to peroxisomal matrix by PTS1 receptor Pex5. Faa2 couples CoA to MCFA to generate MCFA-CoA. Acb1 MCFA-CoA complex travels to plasma membrane through autophagosomes bypassing the vacuoles. The authors also observed that peroxisomal fatty acid β-oxidation as well as PTS2 import pathway is not involved in Acb1 secretion
                This discovery of novel route of secretion is also discussed in Research Highlight in April 2010 issue of Nature Reviews Molecular Cell Biology. Link

Sunday, May 2, 2010

Editorial in Molecular Therapy regarding Gene Therapy

The American Society for Gene & Cell Therapy publishes the journal Molecular Therapy under the auspices of Nature Publishing Group.
The Editorial in May 2010 issue by Dr. Derek Persons is titled "Lentiviral Vector Gene Therapy: Effective and Safe?"
The editor writes about the relative safety issues associated with γ-retroviral or lentiviral vector therapy to treat certain clinical disporders.
He also draws attention to the successful treatment of two X-ALD patients reported by Cartier et al. in Science last year "Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy". X-linked adrenoleukodystrophy is a genetic disorder involving defects in ABCD1 gene which results into deficiency of ATP binding cassette transporter in peroxisomal membrane. This paper was not only of significance to peroxisome field but in general a breakthrough treatment using gene therapy.

Saturday, May 1, 2010

Welcome

PEROXISOME
The organelle belongs to microbody family of organelles which includes glyoxisomes from plants and glycosomes from trypanosomes.
The single membrane bound organelle lacks its own genome and the nuclear encoded proteins are imported post-transaltionally.
Recently some insight has been gained about the biogenesis, maintenance, inheritance and most interestingly the trasnlocation across membrane in native (oligomeric too) form.
This website aims at collecting the peroxisome and related research updates, briefly summarizing the new articles, analyzing the new insights and present it in a easy to read form.

Deveoped by- Vishal Kalel (vishal.kalel@rub.de)