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

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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
Creators:
CreatorsEmailORCIDORCID Put Code
Ban, TadatoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ishihara, TakayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohno, HirotoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saita, ShotaroUNSPECIFIEDorcid.org/0000-0002-7406-8361UNSPECIFIED
Ichimura, AyakaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maenaka, KatsumiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oka, ToshihikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mihara, KatsuyoshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ishihara, NaotadaUNSPECIFIEDorcid.org/0000-0002-6305-7149UNSPECIFIED
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
Uncontrolled Keywords:
KeywordsLanguage
DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; INNER-MEMBRANE-FUSION; PROTEOLYTIC CLEAVAGE; LIPID-COMPOSITION; REQUIRES; GTP; MORPHOLOGY; OLIGOMERS; FISSIONMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22681

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