TY - JOUR
T1 - Systematic multi-level analysis of an organelle proteome reveals new peroxisomal functions
AU - Yifrach, Eden
AU - Holbrook-Smith, Duncan
AU - Bürgi, J. rôme
AU - Othman, Alaa
AU - Eisenstein, Miriam
AU - van Roermund, Carlo Wt
AU - Visser, Wouter
AU - Tirosh, Asa
AU - Rudowitz, Markus
AU - Bibi, Chen
AU - Galor, Shahar
AU - Weill, Uri
AU - Fadel, Amir
AU - Peleg, Yoav
AU - Erdmann, Ralf
AU - Waterham, Hans R.
AU - Wanders, Ronald J. A.
AU - Wilmanns, Matthias
AU - Zamboni, Nicola
AU - Schuldiner, Maya
AU - Zalckvar, Einat
N1 - Funding Information: The work in this manuscript is part of a project that has received funding from the European Research council (ERC) under the European Union's Horizon 2020 research and innovation program (EU-H2020-ERC-CoG; grant name OnTarget, grant number 864068 to M.S.). This project was also supported by an Israeli Science Foundation grant ISF 914/22 and through the generous support of the Kekst Family Institute for Medical Genetics. The robotic system of the Schuldiner Lab was purchased through the kind support of the Blythe Brenden-Mann Foundation. MS is an Incumbent of Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. EY is supported by the Ariane de Rothschild Women Doctoral Program. We thank Renate Maier and Prof. Bettina Warscheid for kindly sharing the CB199 strain that was used for the growth assays and Dr. Michal Skruzny for sharing the mScarlet tagging plasmid. We also thank Prof. Oren Schuldiner and Dr. Noa Dahan for critically reviewing the paper. Publisher Copyright: © 2022 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Seventy years following the discovery of peroxisomes, their complete proteome, the peroxi-ome, remains undefined. Uncovering the peroxi-ome is crucial for understanding peroxisomal activities and cellular metabolism. We used high-content microscopy to uncover peroxisomal proteins in the model eukaryote - Saccharomyces cerevisiae. This strategy enabled us to expand the known peroxi-ome by ~40% and paved the way for performing systematic, whole-organellar proteome assays. By characterizing the sub-organellar localization and protein targeting dependencies into the organelle, we unveiled non-canonical targeting routes. Metabolomic analysis of the peroxi-ome revealed the role of several newly identified resident enzymes. Importantly, we found a regulatory role of peroxisomes during gluconeogenesis, which is fundamental for understanding cellular metabolism. With the current recognition that peroxisomes play a crucial part in organismal physiology, our approach lays the foundation for deep characterization of peroxisome function in health and disease.
AB - Seventy years following the discovery of peroxisomes, their complete proteome, the peroxi-ome, remains undefined. Uncovering the peroxi-ome is crucial for understanding peroxisomal activities and cellular metabolism. We used high-content microscopy to uncover peroxisomal proteins in the model eukaryote - Saccharomyces cerevisiae. This strategy enabled us to expand the known peroxi-ome by ~40% and paved the way for performing systematic, whole-organellar proteome assays. By characterizing the sub-organellar localization and protein targeting dependencies into the organelle, we unveiled non-canonical targeting routes. Metabolomic analysis of the peroxi-ome revealed the role of several newly identified resident enzymes. Importantly, we found a regulatory role of peroxisomes during gluconeogenesis, which is fundamental for understanding cellular metabolism. With the current recognition that peroxisomes play a crucial part in organismal physiology, our approach lays the foundation for deep characterization of peroxisome function in health and disease.
KW - Saccharomyces cerevisiae
KW - high-content screen
KW - high-resolution imaging
KW - peroxisome
KW - protein targeting
UR - http://www.scopus.com/inward/record.url?scp=85138623210&partnerID=8YFLogxK
U2 - https://doi.org/10.15252/msb.202211186
DO - https://doi.org/10.15252/msb.202211186
M3 - Article
C2 - 36164978
SN - 1744-4292
VL - 18
SP - e11186
JO - Molecular systems biology
JF - Molecular systems biology
IS - 9
M1 - e11186
ER -