Universität zu Köln

Anding, Allyson L., Wang, Chunxin ORCID: 0000-0001-6015-6806, Chang, Tsun-Kai, Sliter, Danielle A., Powers, Christine M., Hofmann, Kay ORCID: 0000-0002-2289-9083, Youle, Richard J. and Baehrecke, Eric H. (2018). Vps13D Encodes a Ubiquitin-Binding Protein that Is Required for the Regulation of Mitochondrial Size and Clearance. Curr. Biol., 28 (2). S. 287 - 302. CAMBRIDGE: CELL PRESS. ISSN 1879-0445

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Abstract

The clearance of mitochondria by autophagy, mitophagy, is important for cell and organism health [1], and known to be regulated by ubiquitin. During Drosophila intestine development, cells undergo a dramatic reduction in cell size and clearance of mitochondria that depends on autophagy, the E1 ubiquitin-activating enzyme Uba1, and ubiquitin [2]. Here we screen a collection of putative ubiquitin-binding domain-encoding genes for cell size reduction and autophagy phenotypes. We identify the endosomal sorting complex required for transport (ESCRT) components TSG101 and Vps36, as well as the novel gene Vps13D. Vps13D is an essential gene that is necessary for autophagy, mitochondrial size, and mitochondrial clearance in Drosophila. Interestingly, a similar mitochondrial phenotype is observed in VPS13D mutant human cells. The ubiquitin-associated (UBA) domain of Vps13D binds K63 ubiquitin chains, and mutants lacking the UBA domain have defects in mitochondrial size and clearance and exhibit semi-lethality, highlighting the importance of Vps13D ubiquitin binding in both mitochondrial health and development. VPS13D mutant cells possess phosphorylated DRP1 and mitochondrial fission factor (MFF) as well as DRP1 association with mitochondria, suggesting that VPS13D functions downstream of these known regulators of mitochondrial fission. In addition, the large Vps13D mitochondrial and cell size phenotypes are suppressed by decreased mitochondrial fusion gene function. Thus, these results provide a previously unknown link between ubiquitin, mitochondrial size regulation, and autophagy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Anding, Allyson L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Chunxin UNSPECIFIED orcid.org/0000-0001-6015-6806 UNSPECIFIED Chang, Tsun-Kai UNSPECIFIED UNSPECIFIED UNSPECIFIED Sliter, Danielle A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Powers, Christine M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Youle, Richard J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baehrecke, Eric H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-198597
DOI:	10.1016/j.cub.2017.11.064
Journal or Publication Title:	Curr. Biol.
Volume:	28
Number:	2
Page Range:	S. 287 - 302
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1879-0445
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 AUTOPHAGY; DROSOPHILA; RECOGNITION; GENES; DEGRADATION; FISSION; GENOME Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19859