Mitochondrial dynamics: overview of molecular mechanisms

By Lisa Tilokani, Shun Nagashima, Vincent Paupe, J. Prudent. Essays in Biochemistry, 2018

1,096 citations recorded by the source corpus.

Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, in order to maintain their shape, distribution and size. Their transient and rapid morphological adaptations are crucial for many cellular processes such as cell cycle, immunity, apoptosis and mitochondrial quality control. Mutations in the core machinery components and defects in mitochondrial dynamics have been associated with numerous human diseases. These dynamic transitions are mainly ensured by large GTPases belonging to the Dynamin family. Mitochondrial fission is a multi-step process allowing the division of one mitochondrion in two daughter mitochondria. It is regulated by the recruitment of the GTPase Dynamin-related protein 1 (Drp1) by adaptors at actin- and endoplasmic reticulum-mediated mitochondrial constriction sites. Drp1 oligomerization followed by mitochondrial constriction leads to the recruitment of Dynamin 2 to terminate membrane scission. Inner mitochondrial membrane constriction has been proposed to be an independent process regulated by calcium influx. Mitochondrial fusion is driven by a two-step process with the outer mitochondrial membrane fusion mediated by mitofusins 1 and 2 followed by inner membrane fusion, mediated by optic atrophy 1. In addition to the role of membrane lipid composition, several members of the machinery can undergo post-translational modifications modulating these processes. Understanding the molecular mechanisms controlling mitochondrial dynamics is crucial to decipher how mitochondrial shape meets the function and to increase the knowledge on the molecular basis of diseases associated with morphology defects. This article will describe an overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals.

Subfields: Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/654586e4257a39032b7bd6ac915416c8db7b79a3

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Citations in the corpus

• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “17 In brief, fi ssion contributes to mitochondrial quality control by elimination of impaired or dysfunctional mitochondria, and promotes apoptosis facing the severe cellular stress, while fusion is conducive to mix and exchange the intramitochondrial contents between mitochondria, these help to…”
• Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “94 To reach the mitochondrial matrix, cytosolic Ca 2 + has to cross the IMM, mainly through the mitochondrial Ca 2 + uniporter (MCU) complex.”