Relationship between OPA1 and cardiolipin in mitochondrial inner-membrane fusion
Relationship between OPA1 and cardiolipin in mitochondrial inner-membrane fusion
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DOI：
10.1016/j.bbabio.2018.05.016
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发表时间：
2018-09-01
影响因子：
4.3
通讯作者：
Ishihara, Naotada
中科院分区：
文献类型：
--
作者：
Ban, Tadato;Kohno, Hiroto;Ishihara, Naotada
线粒体是高度动态的细胞器，经历频繁的融合和分裂。大GT视神经萎缩1（OPAL）被确定为内膜（IM）融合的核心组成部分。OPAL以膜锚定的L-OPAL和蛋白水解裂解的可溶性S-OPAL的形式存在。最近，我们发现OPAL和位于心磷脂（CL）的脂质在异型IM融合中协同作用[Ban et al.，19（2017）856-863]。我们使用纯化的人L-OPAL和家蚕中表达的S-OPA 1重建了体外膜融合反应，发现膜一侧的L-OPAL和另一侧的CL足以进行线粒体融合。L-OPAL是异型融合中主要的融合倾向因子。然而，S-OPAL的作用仍然未知，因为S-OPAL促进L-OPAL依赖的异型膜融合和含同型CL的膜融合，但单独的S-OPA 1不足以促进异型膜融合。在活细胞中证实了L-OPAL和CL介导的异型线粒体融合，但Barth综合征的致病基因产物tafazzin（Taz 1）对线粒体融合并不重要。Taz 1依赖的CL成熟可能在线粒体DNA类核的重塑中发挥其他作用。
Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. The large GTPase optic atrophy 1 (OPAL) is identified as a core component of inner membrane (IM) fusion. OPAL exists as the membrane-anchored L-OPAL and the proteolytically cleavage soluble S-OPAL. Recently, we showed that OPAL 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-OPAL and S-OPA1 expressed in silkworm and found that L-OPAL on one side of the membrane and CL on the other side were sufficient for mitochondrial fusion. L-OPAL is the major fusion-prone factor in heterotypic fusion. However, the role of S-OPAL remains unknown as S-OPAL promoted L-OPAL-dependent heterotypic membrane fusion and homotypic CL-containing membrane fusion, but S-OPA1 alone was not sufficient for heterotypic membrane fusion. L-OPAL- 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.