Universität zu Köln

Korwitz, Anne, Merkwirth, Carsten ORCID: 0000-0001-8895-3495, Richter-Dennerlein, Ricarda, Troeder, Simon E., Sprenger, Hans-Georg, Quiros, Pedro M., Lopez-Otin, Carlos ORCID: 0000-0001-6964-1904, Rugarli, Elena I. ORCID: 0000-0002-5782-1067 and Langer, Thomas ORCID: 0000-0003-1250-1462 (2016). Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria. J. Cell Biol., 212 (2). S. 157 - 167. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondria! morphology under stress and in disease. Stress-induced OPA1 processing by OMA1 triggersmitochondrial fragmentation, which is associated with mitophagy and apoptosis in vitro. Here, we identify OMA1 as a critical regulator of neuronal survival in vivo and demonstrate that stress-induced OPA1 processing by OMA1 promotes neuronal death and neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds as a model of neurodegeneration, we demonstrate that additional ablation of Oma 1 delays neuronal loss and prolongs lifespan. This is accompanied by the accumulation of fusion-active, long OPA1 forms, which stabilize the mitochondrial genome but do not preserve mitochondrial cristae or respiratory chain supercomplex assembly in prohibitin-depleted neurons. Thus, long OPA1 forms can promote neuronal survival independently of cristae shape, whereas stress-induced OMA1 activation and OPA1 cleavage limit mitochondrial fusion and promote neuronal death.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Korwitz, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkwirth, Carsten UNSPECIFIED orcid.org/0000-0001-8895-3495 UNSPECIFIED Richter-Dennerlein, Ricarda UNSPECIFIED UNSPECIFIED UNSPECIFIED Troeder, Simon E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprenger, Hans-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Quiros, Pedro M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lopez-Otin, Carlos UNSPECIFIED orcid.org/0000-0001-6964-1904 UNSPECIFIED Rugarli, Elena I. UNSPECIFIED orcid.org/0000-0002-5782-1067 UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-287167
DOI:	10.1083/jcb.201507022
Journal or Publication Title:	J. Cell Biol.
Volume:	212
Number:	2
Page Range:	S. 157 - 167
Date:	2016
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 CYTOCHROME-C RELEASE; INNER-MEMBRANE-FUSION; PROTEOLYTIC CLEAVAGE; PROTEASE OMA1; OXIDATIVE-PHOSPHORYLATION; CRISTAE MORPHOGENESIS; CELL-PROLIFERATION; PROHIBITINS; APOPTOSIS; FISSION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28716