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Mitochondrial Fusion: The Machineries In and Out, Trends Cell Biol, 19 Oct 2020

发布时间:2020年10月19日

Trends in Cell Biology, 19 October, 2020, DOI:https://doi.org/10.1016/j.tcb.2020.09.008

Mitochondrial Fusion: The Machineries In and Out

Song Gao and Junjie Hu

Highlights

Crystal structures of truncated mitofusin (MFN)1 and MFN2, the dynamin-like fusogens of the outer mitochondrial membrane, reveal their structural kinship to bacterial dynamin-like protein (BDLP). Human MFN1 and MFN2 bear subtle differences that govern the distinct biochemical properties.

GTP-dependent dimerization and conformational changes are key features of MFNs in driving outer membrane fusion.

Short optic atrophy 1/short mitochondria genome maintenance 1 (s-OPA1/s-Mgm1) resembles fission dynamins in 3D architecture, highlighting a mechanism of inner mitochondrial membrane (IMM) merging distinct from that of other known types of homotypic fusion.

OPA1/Mgm1 uses multiple intermolecular assemblies to achieve either IMM fusion or cristae shaping.

Structures of the mitochondrial fusion machinery provide important rules for comparing fusion DLPs with fission DLPs.

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion. Disruption of mitochondrial dynamics undermines their function and causes several human diseases. The fusion of the outer (OMM) and inner mitochondrial membranes (IMM) is mediated by two classes of dynamin-like protein (DLP): mitofusin (MFN)/fuzzy onions 1 (Fzo1) and optic atrophy 1/mitochondria genome maintenance 1 (OPA1/Mgm1). Given the lack of structural information on these fusogens, the molecular mechanisms underlying mitochondrial fusion remain unclear, even after 20 years. Here, we review recent advances in structural studies of the mitochondrial fusion machinery, discuss their implication for DLPs, and summarize the pathogenic mechanisms of disease-causing mutations in mitochondrial fusion DLPs.

文章链接:https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(20)30188-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0962892420301884%3Fshowall%3Dtrue

 

 

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