Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8298560 | Biochimica et Biophysica Acta (BBA) - Bioenergetics | 2018 | 28 Pages |
Abstract
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
DDMMfnsHVJMFFNBD-PEBombyx mori nucleopolyhedrovirusGTPaseDrp1SNAREsiRNAsBmNPVMEFMitochondrial DNAopa1Heptad repeatRNAismall interfering RNAsoptic atrophy 1Fluorescence resonance energy transferFRETRh-PETafazzindodecyl maltosidemtDNAendoplasmic reticulumMembrane fissionOuter membraneinner membranemitochondrial fission factorphosphatidylinositolphosphatidylcholinephosphatidylethanolamineRNA-mediated interferencemouse embryonic fibroblastmitofusinsKnockdownknockoutHemagglutinating virus of JapanProteoliposomedynamin-related protein 1Cardiolipinquality controlsoluble N-ethylmaleimide-sensitive factor attachment protein receptor
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Authors
Tadato Ban, Hiroto Kohno, Takaya Ishihara, Naotada Ishihara,