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

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2017 Jun 20

PMID 28628083

Citations 186

Authors

Tadato Ban

Takaya Ishihara

Hiroto Kohno

Shotaro Saita

Ayaka Ichimura

Katsumi Maenaka

Toshihiko Oka

Katsuyoshi Mihara

Naotada Ishihara

Affiliations

Soon will be listed here.

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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