Universität zu Köln

Anand, Ruchika ORCID: 0000-0001-7337-6007, Wai, Timothy ORCID: 0000-0002-6770-6222, Baker, Michael J., Kladt, Nikolay, Schauss, Astrid C., Rugarli, Elena ORCID: 0000-0002-5782-1067 and Langer, Thomas ORCID: 0000-0003-1250-1462 (2014). The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J. Cell Biol., 204 (6). S. 919 - 930. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage by YME1L and OMA1 at two distinct sites leads to the accumulation of both long and short forms of OPA1 and maintains mitochondrial fusion. Stress-induced OPA1 processing by OMA1 converts OPA1 completely into short isoforms, inhibits fusion, and triggers mitochondrial fragmentation. Here, we have analyzed the function of different OPA1 forms in cells lacking YME1L, OMA1, or both. Unexpectedly, deletion of Oma1 restored mitochondrial tubulation, cristae morphogenesis, and apoptotic resistance in cells lacking YME1L. Long OPA1 forms were sufficient to mediate mitochondrial fusion in these cells. Expression of short OPA1 forms promoted mitochondrial fragmentation, which indicates that they are associated with fission. Consistently, GTPase-inactive, short OPA1 forms partially colocalize with ER-mitochondria contact sites and the mitochondrial fission machinery. Thus, OPA1 processing is dispensable for fusion but coordinates the dynamic behavior of mitochondria and is crucial for mitochondrial integrity and quality control.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Anand, Ruchika UNSPECIFIED orcid.org/0000-0001-7337-6007 UNSPECIFIED Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Baker, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kladt, Nikolay UNSPECIFIED UNSPECIFIED UNSPECIFIED Schauss, Astrid C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rugarli, Elena UNSPECIFIED orcid.org/0000-0002-5782-1067 UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443303
DOI:	10.1083/jcb.201308006
Journal or Publication Title:	J. Cell Biol.
Volume:	204
Number:	6
Page Range:	S. 919 - 930
Date:	2014
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
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 DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; CYTOCHROME-C RELEASE; CRISTAE MORPHOGENESIS; PROTEOLYTIC CLEAVAGE; CELL-PROLIFERATION; MAMMALIAN-CELLS; APOPTOSIS; MORPHOLOGY; DIVISION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/44330