Relationship between OPA1 and cardiolipin in mitochondrial inner-membrane fusion

Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):951-957. doi: 10.1016/j.bbabio.2018.05.016. Epub 2018 May 28.


Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. The large GTPase optic atrophy 1 (OPA1) is identified as a core component of inner membrane (IM) fusion. OPA1 exists as the membrane-anchored L-OPA1 and the proteolytically cleavage soluble S-OPA1. Recently, we showed that OPA1 and mitochondria-localized lipid cardiolipin (CL) cooperate in heterotypic IM fusion [Ban et al., Nat. Cell Biol. 19 (2017) 856-863]. We reconstituted an in vitro membrane fusion reaction using purified human L-OPA1 and S-OPA1 expressed in silkworm and found that L-OPA1 on one side of the membrane and CL on the other side were sufficient for mitochondrial fusion. L-OPA1 is the major fusion-prone factor in heterotypic fusion. However, the role of S-OPA1 remains unknown as S-OPA1 promoted L-OPA1-dependent heterotypic membrane fusion and homotypic CL-containing membrane fusion, but S-OPA1 alone was not sufficient for heterotypic membrane fusion. L-OPA1- and CL-mediated heterotypic mitochondrial fusion was confirmed in living cells, but tafazzin (Taz1), the causal gene product of Barth syndrome, was not essential for mitochondrial fusion. Taz1-dependent CL maturation might have other roles in the remodeling of mitochondrial DNA nucleoids.

Keywords: GTPase; Membrane fission; Mitochondrial membrane fusion; Proteoliposome; Quality control; Silkworm expression system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiolipins / metabolism*
  • GTP Phosphohydrolases / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Fusion*
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics*


  • Cardiolipins
  • GTP Phosphohydrolases
  • OPA1 protein, human