
Systematic multi‐level analysis of an organelle proteome reveals new peroxisomal functions
Author(s) -
Yifrach Eden,
HolbrookSmith Duncan,
Bürgi Jérôme,
Othman Alaa,
Eisenstein Miriam,
Roermund Carlo WT,
Visser Wouter,
Tirosh Asa,
Rudowitz Markus,
Bibi Chen,
Galor Shahar,
Weill Uri,
Fadel Amir,
Peleg Yoav,
Erdmann Ralf,
Waterham Hans R,
Wanders Ronald J A,
Wilmanns Matthias,
Zamboni Nicola,
Schuldiner Maya,
Zalckvar Einat
Publication year - 2022
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.202211186
Subject(s) - biology , peroxisome , proteome , organelle , computational biology , organelle biogenesis , microbiology and biotechnology , bioinformatics , genetics , biogenesis , gene
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.