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Understanding Peroxisome Functions

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Associate Staff Scientist:

Dr. Einat Zalckvar 

Head of peroxisomes group


Dept. of Molecular Genetics 
Meyer Bldg. Room 122 
Weizmann Institute of Sciences 
Rehovot 7610001, Israel 
Office Tel: +972-8-9529035

The Mysterious Peroxisomes

Research

Peroxisomes are fascinating organelles that are found in almost all eukaryotes. Peroxisomes participate in central pathways of cellular metabolism such as β-oxidation of fatty acids, amino acid catabolism and detoxification of reactive oxygen species as well as in recently identified non-metabolic processes such as antiviral innate immunity. Peroxisomes have complex biogenesis and degradation possibilities, are actively distributed during cell division and possess their own targeting and translocation machineries. Additionally, peroxisomes are remarkably diverse in shape, size, number and content. This diversity depends on the cell type and environment, and can be rapidly regulated in response to diverse signals. Hence, peroxisomes represent a dynamic and complex system that has biological ‘inputs’ and whose biological processes could be modelled with enough information to predict ‘outputs’.

Additionally a large number of peroxisomal disorders with dramatic phenotypes have been described and malfunctions in peroxisomes contribute to the etiology of Alzheimer's and Parkinson's diseases, aging, cancer and type 2 diabetes.

We are using systems cell biology approaches in yeast in an attempt to understand peroxisomes as a complete biological system.

We are specifically interested in:

  1. Identifying new functions of peroxisomes

  2. Discovering new peroxisomal proteins

  3. Identifying peroxisome contact sites with other organelles

  4. Systematically characterizing the peroxisome proteome under different conditions

  5. Further understanding how proteins are targeted to peroxisomes

  6. Identifying the peroxisomal protein quality control machinery

     

     

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ERC CoG 646604

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Team

Peroxisome Team Members

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Dr. Ofir Klein

Postdoctoral fellow

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Lior Peer

PhD Student

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Mor Angel

PhD Student

Olga Beresh

M.Sc Student

Publications

Publications

original research

Determining the targeting specificity of the selective peroxisomal targeting factor Pex9

Eden Yifrach, Markus Rudowitz, Luis Daniel Cruz-Zaragoza, Asa Tirosh, Zohar Gazi, Yoav Peleg, Markus Kunze, Miriam Eisenstein, Wolfgang Schliebs, Maya Schuldiner, Ralf Erdmann, Einat Zalckvar

Systematic multi-level analysis of an organelle proteome reveals new peroxisomal functions

Eden Yifrach, Duncan Holbrook-Smith, Jérôme Bürgi, Alaa Othman, Miriam Eisenstein, Carlo Wt van Roermund, Wouter Visser, Asa Tirosh, Markus Rudowitz, Chen Bibi, Shahar Galor, Uri Weill, Amir Fadel, Yoav Peleg, Ralf Erdmann, Hans R Waterham, Ronald J A Wanders, Matthias Wilmanns, Nicola Zamboni, Maya Schuldiner, Einat Zalckvar

Beyond rare disorders: A new era for peroxisomal pathophysiology

Einat Zalckvar and Maya Schuldiner

​Peroxisome function relies on organelle-associated mRNA translation

Noa Dahan, Yury S Bykov, Elizabeth A Boydston, Amir Fadel, Zohar Gazi, Hodaya Hochberg-Laufer, James Martenson, Vlad Denic, Yaron Shav-Tal, Jonathan S Weissman, Naama Aviram, Einat Zalckvar, Maya Schuldiner

A piggybacking mechanism enables peroxisomal localization
of the glyoxylate cycle enzyme Mdh2 in yeast

Journal of Cell Science 2020

Shiran Gabay-Maskit, Luis Daniel Cruz-Zaragoza, Nadav Shai, Miriam Eisenstein, Chen Bibi,
Nir Cohen, Tobias Hansen, Eden Yifrach, Nofar Harpaz, Ruth Belostotsky, Wolfgang Schliebs,
Maya Schuldiner, Ralf Erdmann and Einat Zalckvar

Pex14p Phosphorylation Modulates Import of Citrate Synthase 2 Into Peroxisomes in Saccharomyces cerevisiae

Front Cell Dev Biol 2020 August

Uncovering targeting priority to yeast peroxisomes using an in-cell competition assay.

PNAS, 2020 Aug

Rosenthal M, Metzl-Raz E, Bürgi J, Yifrach E, Drwesh L, Fadel A, Peleg Y, Rapaport D, Wilmanns M, Barkai N, Schuldiner M, Zalckvar E.

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii

Genes 2018

Alison J. Mbekeani , Will A. Stanley , Vishal C. Kalel , Noa Dahan , Einat Zalckvar , Lilach Sheiner  , Wolfgang Schliebs , Ralf Erdmann , Ehmke Pohl  and Paul W. Denny 

An alternative membrane topology permits lipid droplet localization of peroxisomal fatty acyl-CoA reductase 1

J Cell Sci 2019

Tarik Exner, Inés Romero-Brey, Eden Yifrach, Jhon Rivera-Monroy, Bianca Schrul, Christos C. Zouboulis, Wolfgang Stremmel, Masanori Honsho, Ralf Bartenschlager, Einat Zalckvar, Margarete Poppelreuther, Joachim Füllekrug

Genome-wide SWAp-Tag yeast libraries for proteome exploration

Nat Methods. 2018 Jul

Weill U, Yofe I, Sass E, Stynen B, Davidi D, Natarajan J, Ben-Menachem R, Avihou Z, Goldman O, Harpaz N, Chuartzman S, Kniazev K, Knoblach B, Laborenz J, Boos F, Kowarzyk J, Ben-Dor S, Zalckvar E, Herrmann JM, Rachubinski RA, Pines O, Rapaport D, Michnick SW, Levy ED, Schuldiner M.

Validation of a yeast malate dehydrogenase 2 (Mdh2) antibody tested for use in western blots

Nat Methods. 2018 Jul

​Gabay-Maskit S, Schuldiner M, Zalckvar E.

Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact

Nat Commun. 2018 May

Shai N, Yifrach E, van Roermund CWT, Cohen N, Bibi C, IJlst L, Cavellini L, Meurisse J, Schuster R, Zada L, Mari MC, Reggiori FM, Hughes AL, Escobar-Henriques M, Cohen MM, Waterham HR, Wanders RJA, Schuldiner M and Zalckvar E.

Saccharomyces cerevisiae cells lacking Pex3 contain membrane vesicles that harbor a subset of peroxisomal membrane proteins

Biochim Biophys Acta. 2017

Wroblewska JP, Cruz-Zaragoza LD, Wei Y, Schummer A, Chuartzman SG, de Boer R, Oeljeklaus S, Schuldiner M, Zalckvar E, Warscheid B, Erdmann R, van der Klei IJ.

Pex35 is a regulator of peroxisome abundance

J Cell Sci. 2017

Yofe I, Soliman K, Chuartzman SG, Morgan B, Weill U, Yifrach E, Dick TP, Cooper SJ, Ejsing CS, Schuldiner M, Zalckvar E, Thoms S.

Characterization of proteome dynamics in oleate reveals a novel peroxisome targeting receptor

J Cell Sci. 2016

Yifrach E, Chuartzman SG, Dahan N, Maskit S, Zada L, Weill U, Yofe I, Olender T, Schuldiner M, Zalckvar E.

One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy

Nat Methods. 2016

Yofe I, Weill U, Meurer M, Chuartzman S, Zalckvar E, Goldman O, Ben-Dor S, Schütze C, Wiedemann N, Knop M, Khmelinskii A, Schuldiner M.

 

The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects glutathione redox homeostasis. 

FEMS Yeast Res. 2014

Elbaz-Alon Y, Morgan B, Clancy A, Amoako TN, Zalckvar E, Dick TP, Schwappach B, Schuldiner M. 

FEMS Yeast Res. 2014

Peroxisomes are juxtaposed to strategic sites on mitochondria. 

Mol Biosyst. 2014

Cohen Y, Klug YA, Dimitrov L, Erez Z, Chuartzman SG, Elinger D, Yofe I, Soliman K, Gärtner J, Thoms S, Schekman R, Elbaz-Alon Y, Zalckvar E, Schuldiner M.

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Reviews and book chapters

Defining the Mammalian Peroxisomal Proteome

Subcell Biochem. 2018

Eden Yifrach, Sven Fischer, Silke Oeljeklaus, Maya Schuldiner,
Einat Zalckvar and Bettina Warscheid

Mind the Organelle Gap – Peroxisome Contact Sites in Disease

Trends in Biochemical Sciences. 2018 Jan

Castro G. I., Schuldiner M., Zalckvar E.

 

Peroxisome Mini-Libraries: Systematic Approaches to Study Peroxisomes Made Easy

Methods Mol Biol. 2017

​Dahan N, Schuldiner M and Zalckvar E.

No peroxisome is an island - Peroxisome contact sites.

Biochim Biophys Acta. 2015

Shai N, Schuldiner M, Zalckvar E.

 

Peroxisystem: harnessing systems cell biology to study peroxisomes.

Biol Cell. 2015

Schuldiner M, Zalckvar E.

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OEPM 2018

20181026_165618
IMG_20181026_135945
20181025_150423
IMG-20181027-WA0033
20181025_145308
New Horizons

New Horizons in Peroxisome Biology - Israel 2018

peroxi pictures
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Pictures by: Michal Eisenberg-Bord,  Matthias Wilmanns
Peroxisystem

Peroxisystem meeting - Israel 2016

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Pictures by: Michal Eisenberg-Bord
Peroxi-club
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Coming Up

October 12th 2023, 4pm (Israel time)

TBD

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Previous Talks

October 2022

The role of ether phospholipids in neurodevelopmental and neurodegenerative disorders

Prof. Johannes Berger, Medical University of Viena, Austria

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July 2022

Structure of the peroxisomal retro-translocon formed by a heterotrimeric ubiquitin ligase complex

Dr. Peiqiang Feng, Rapoport group, Harvard Medical School/HHMI, USA

June 2022

Zebrafish peroxisomes

Dr. Quentin Raas, Bonkowsky group, University of Utah, USA

April 2022

Gene Therapy for Zellweger Spectrum Disorder

Dr. Catherine Argyriou,  Braverman group, McGill University, Canada

February 2022​

Peroxisomal disorders

Dr. Femke Klouwer,  AMC, Amsterdam

December 2021

Fly peroxisomes

Dr. Francesca Di Cara, Dalhousie University, Canada

September 2021

Peroxisome engineering

Dr. Ka-Hei Sui, Dueber group, Berkeley, USA

July 2021

Peroxisomes and parasites

Dr. Vishal Kalel, Erdmann group, Bochum, Germany

May 2021

Peroxisomes and viruses

Dr. Daniela Ribeiro, University of Aveiro, Portugal

March 2021 

Plant peroxisomes

Dr. Zachary Wright, Bartel group, Rice University, USA

January 2021 

Peroxisome contact sites

Dr. Joseph Costello, University of Exeter, UK

November 2020

Protein targeting to the peroxisome matrix

Dr. Jérôme Bürgi, Wilmanns group, European Molecular Biology Laboratory (EMBL), Germany

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December 2022

Family, Research, and HOPE - The mission of The Global Foundation for Peroxisomal Disorders

Melissa Bryce, Executive Director, The Global Foundation for Peroxisomal Disorders

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February 2023

Peroxisome stress responses in c.elegans

Dr. Tomer Shpilka, Haynes group, UMass Chan Medical School. USA

April 2023

Upregulated pexophagy limits the degradative capacity of selective autophagy

Kyla Germain, Kim group, University of Toronto & The Hospital for Sick Children

June 2023

Peroxisome dynamics in health and disease

Dr. Ruth Carmichael, Schrader group, University of Exeter

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