Universität zu Köln

Simoes, Tania, Schuster, Ramona ORCID: 0000-0002-2227-3718, den Brave, Fabian ORCID: 0000-0001-6955-4616 and Escobar-Henriques, Mafalda ORCID: 0000-0002-0879-3119 (2018). Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion. eLife, 7. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Cdc48/p97, a ubiquitin-selective chaperone, orchestrates the function of E3 ligases and deubiquitylases (DUBs). Here, we identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. The DUBs Ubp12 and Ubp2 exert opposing effects on mitochondrial fusion and cleave different ubiquitin chains on the mitofusin Fzo1. We demonstrate that Cdc48 integrates the activities of these two DUBs, which are themselves ubiquitylated. First, Cdc48 promotes proteolysis of Ubp12, stabilizing pro-fusion ubiquitylation on Fzo1. Second, loss of Ubp12 stabilizes Ubp2 and thereby facilitates removal of ubiquitin chains on Fzo1 inhibiting fusion. Thus, Cdc48 synergistically regulates the ubiquitylation status of Fzo1, allowing to control the balance between activation or repression of mitochondrial fusion. In conclusion, we unravel a new cascade of ubiquitylation events, comprising Cdc48 and two DUBs, fine-tuning the fusogenic activity of Fzo1.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Simoes, Tania UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuster, Ramona UNSPECIFIED orcid.org/0000-0002-2227-3718 UNSPECIFIED den Brave, Fabian UNSPECIFIED orcid.org/0000-0001-6955-4616 UNSPECIFIED Escobar-Henriques, Mafalda UNSPECIFIED orcid.org/0000-0002-0879-3119 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-199049
DOI:	10.7554/eLife.30015
Journal or Publication Title:	eLife
Volume:	7
Date:	2018
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BOUND TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; DEUBIQUITINATING ENZYME; DEPENDENT DEGRADATION; OXIDATIVE STRESS; MEMBRANE-FUSION; SHUTTLE VECTORS; PROTEIN; PROTEASOME; MITOFUSIN Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19904