Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin.
Nat Cell Biol
; 19(7): 856-863, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28628083
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. 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. 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.
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Base de dados:
MEDLINE
Assunto principal:
Cardiolipinas
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Membranas Mitocondriais
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Dinâmica Mitocondrial
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GTP Fosfo-Hidrolases
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Mitocôndrias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article