The molecular mechanism and cellular functions of mitochondrial division

Abstract

Mitochondria are highly dynamic organelles that continuously divide and fuse. These dynamic processes regulate the size, shape, and distribution of the mitochondrial network. In addition, mitochondrial division and fusion play critical roles in cell physiology. This review will focus on the dynamic process of mitochondrial division, which is highly conserved from yeast to humans. We will discuss what is known about how the essential components of the division machinery function to mediate mitochondrial division and then focus on proteins that have been implicated in division but whose functions remain unclear. We will then briefly discuss the cellular functions of mitochondrial division and the problems that arise when division is disrupted.

Figure 1. The cellular distribution of Dnm1 and Drp1

A) In yeast, Dnm1 is predominantly found in self-assembled structures, a majority of which are associated with mitochondria. B and C) Under normal growth conditions (B and B′), the bulk of Drp1 in COS cells is diffusely dispersed in the cytosol with only a small fraction of the protein found assembled on mitochondria. Following STS treatment (C and C′), the assembly and mitochondrial targeting of Drp1 are markedly increased resulting in increased mitochondrial division and fragmentation. Panels B′ and C′ are a representative region of each cell shown in panels B and C and are magnified 7-fold. Dnm1 and Drp1 are shown in green and mitochondria are shown in red. Panels B, B′, C and C′ are reproduced from Cassidy- Stone et al. 2008, Developmental Cell [95]. Scale bars: (A) 1 μm, (B and C) 10 μm, (B′and C′) 1 μm.

Figure 2. A model of Dnm1/Drp1-driven mitochondrial division

Dnm1/Drp1-driven mitochondrial division can be broken down into 3 stages: targeting, assembly-driven constriction, and hydrolysis-mediated constriction/scission. Briefly, Dnm1/Drp1 is first targeted to the mitochondrial surface. Once targeted, Dnm1/Drp1 undergoes GTP-driven assembly into a helical structure, which drives the constriction of the mitochondrial tubule. GTP-driven assembly also stimulates nucleotide hydrolysis which is likely to evoke additional conformational changes in the Dnm1 helix that are required for further constriction and subsequent scission of the mitochondrial membranes. Dnm1/Drp1 is shown in red and a portion of a mitochondrial tubule is shown in green.