Ban, Tadato, Ishihara, Takaya, Kohno, Hiroto, Saita, Shotaro ORCID: 0000-0002-7406-8361, Ichimura, Ayaka, Maenaka, Katsumi, Oka, Toshihiko, Mihara, Katsuyoshi and Ishihara, Naotada ORCID: 0000-0002-6305-7149 (2017). Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin. Nat. Cell Biol., 19 (7). S. 856 - 870. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4679
Full text not available from this repository.Abstract
Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. Optic atrophy 1 (OPA1) is an essential GTPase protein for both mitochondrial inner membrane (IM) fusion and cristae morphology(1,2). Under mitochondria-stress conditions, membrane-anchored L-OPA1 is proteolytically cleaved to form peripheral S-OPA1, leading to the selection of damaged mitochondria for mitophagy(2-4). However, molecular details of the selective mitochondrial fusion are less well understood. Here, we showed that L-OPA1 and cardiolipin (CL) cooperate in heterotypic mitochondrial IM fusion. We reconstituted an in vitro membrane fusion reaction using purified human L-OPA1 protein expressed in silkworm, and found that L-OPA1 on one side of the membrane and CL on the other side are sufficient for fusion. GTP-independent membrane tethering through L-OPA1 and CL primes the subsequent GTP-hydrolysis-dependent fusion, which can be modulated by the presence of S-OPA1. These results unveil the most minimal intracellular membrane fusion machinery. In contrast, independent of CL, a homotypic trans-OPA1 interaction mediates membrane tethering, thereby supporting the cristae structure. Thus, multiple OPA1 functions are modulated by local CL conditions for regulation of mitochondrial morphology and quality control.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-226810 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/ncb3560 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Cell Biol. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 19 | ||||||||||||||||||||||||||||||||||||||||
Number: | 7 | ||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 856 - 870 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2017 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1476-4679 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/22681 |
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