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J Cell Sci. 2016 Jun 15;129(12):2297-306. doi: 10.1242/jcs.159186. Epub 2016 May 17.

OPA1 processing in cell death and disease - the long and short of it.

Author information

1
Institute of Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne, Cologne 50931, Germany.
2
Institute of Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne, Cologne 50931, Germany thomas.langer@uni-koeln.de.

Abstract

The regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and preserving cellular health. OPA1 governs the delicate balance between fusion and fission in the dynamic mitochondrial network. A disturbance of this balance, often observed under stress and pathologic conditions, causes mitochondrial fragmentation and can ultimately result in cell death. As discussed in this Commentary, these morphological changes are regulated by proteolytic processing of OPA1 by the inner-membrane peptidases YME1L (also known as YME1L1) and OMA1. Long, membrane-bound forms of OPA1 are required for mitochondrial fusion, but their processing to short, soluble forms limits fusion and can facilitate mitochondrial fission. Excessive OPA1 processing by the stress-activated protease OMA1 promotes mitochondrial fragmentation and, if persistent, triggers cell death and tissue degeneration in vivo The prevention of OMA1-mediated OPA1 processing and mitochondrial fragmentation might thus offer exciting therapeutic potential for human diseases associated with mitochondrial dysfunction.

KEYWORDS:

Mitochondria; Mitochondrial cristae; Mitochondrial dynamics; Mitochondrial fusion; OPA1; OPA1 processing

PMID:
27189080
DOI:
10.1242/jcs.159186
[Indexed for MEDLINE]
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