Ubiquitin ligase MARCH5 localizes to peroxisomes to regulate pexophagy

• Published in: The Journal of cell biology Vol. 221; no. 1
• Main Authors: Zheng, Jun, Chen, Xi, Liu, Qiang, Zhong, Guisheng, Zhuang, Min
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 03.01.2022
• Subjects: ATP-Binding Cassette Transporters - metabolism; Biochemistry; Blood Proteins - pharmacology; Cell Death and Autophagy; HeLa Cells; Humans; Jurkat Cells; Lipoproteins - metabolism; Macroautophagy - drug effects; Membrane Proteins - metabolism; Mitochondria; Organelles; Peroxins - metabolism; Peroxisomes; Peroxisomes - drug effects; Peroxisomes - metabolism; Pexophagy; Protein Binding - drug effects; Protein Transport - drug effects; Proteins; Quality control; TOR protein; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.202103156

Mitochondria and peroxisomes are independent but functionally closely related organelles. A few proteins have been characterized as dual-organelle locating proteins with distinct or similar roles on mitochondria and peroxisomes. MARCH5 is a mitochondria-associated ubiquitin ligase best known for its regulatory role in mitochondria quality control, fission, and fusion. Here, we used a proximity tagging system, PUP-IT, and identified new interacting proteins of MARCH5. Our data uncover that MARCH5 is a dual-organelle locating protein that interacts with several peroxisomal proteins. PEX19 binds the transmembrane region on MARCH5 and targets it to peroxisomes. On peroxisomes, MARCH5 binds and mediates the ubiquitination of PMP70. Furthermore, we find PMP70 ubiquitination and pexophagy induced by mTOR inhibition are blocked in the absence of MARCH5. Our study suggests novel roles of MARCH5 on peroxisomes.