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. 2017 Jul;19(7):856-863.
doi: 10.1038/ncb3560. Epub 2017 Jun 19.

Molecular Basis of Selective Mitochondrial Fusion by Heterotypic Action Between OPA1 and Cardiolipin

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Molecular Basis of Selective Mitochondrial Fusion by Heterotypic Action Between OPA1 and Cardiolipin

Tadato Ban et al. Nat Cell Biol. .

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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References

    1. Nat Genet. 2000 Oct;26(2):207-10 - PubMed
    1. Nat Cell Biol. 2000 Oct;2(10):754-61 - PubMed
    1. Annu Rev Biochem. 2001;70:777-810 - PubMed
    1. Nature. 2003 May 29;423(6939):537-41 - PubMed
    1. J Biochem. 2003 Sep;134(3):333-44 - PubMed

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