Mitochondrial fission and fusion

Abstract

Mitochondria are highly dynamic cellular organelles, with the ability to change size, shape and position over the course of a few seconds. Many of these changes are related to the ability of mitochondria to undergo the highly co-ordinated processes of fission (division of a single organelle into two or more independent structures) or fusion (the opposing reaction). These actions occur simultaneously and continuously in many cell types, and the balance between them regulates the overall morphology of mitochondria within any given cell. Fission and fusion are active processes which require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and adaptor proteins that regulate the interaction of these mechanical proteins with organelles. Although not fully understood, alterations in mitochondrial morphology appear to be involved in several activities that are crucial to the health of cells. In the present chapter we discuss the mechanisms behind mitochondrial fission and fusion, and discuss the implications of changes in organelle morphology during the life of a cell.

Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission

“…It should be noted that these are similar to the challenge faced by mitochondria, in that mitochondria can be similar in size to the annular gap junction vesicles, and they, like the gap junction structures, are double membrane-bound organelles. Mitochondria frequently divide and the molecular machinery involved in mitochondrial fissions has been well established (Elgass et al, 2013;Hoppins et al, 2007;Scott and Youle, 2010). During mitochondrial fissions two members of the dynamin superfamily, dynamin-related proteins (Dnm1) in yeast, and dynamin-related protein (DRP 1) in mammals, assemble into punctate structures on mitochondria surfaces.…”

Multistep and multitask Bax activation

“…During apoptosis, the mitochondrial network collapses, due to excess of fission and inhibition of fusion (Polyakov et al, 2003). Bax is strongly implicated in this phenomenon; it is present at fission sites in apoptosis (Karbowski et al, 2002); its overexpression or re-introduction into Bax null cells accelerates (Scott and Youle, 2010) mitochondrial collapse, and activated Bax in apoptosis binds to proteins of the mitochondrial fission machinery (Suen et al, 2008). Kinetics and spatial evidences link mitochondrial fission in apoptosis with the release of cytochrome c, but there is no consensus as to whether these events are causally linked; in fact, recent evidences dissociate the two phenomena, suggesting that they are due to different Bax functions (Parone et al, 2006;Sheridan et al, 2008).…”

Novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity

“…This dynamic process controls not only mitochondrial morphology, but also the subcellular location and function of mitochondria. Defects in either fusion or fission limit mitochondrial motility, decrease energy production and increase oxidative stress, thereby promoting cell dysfunction and death (Jahani-Asl et al, 2010;Scott and Youle, 2010). The two opposing processes, fusion and fission, are controlled by evolutionarily conserved large GTPases that belong to the dynamin family of proteins.…”

“…The two opposing processes, fusion and fission, are controlled by evolutionarily conserved large GTPases that belong to the dynamin family of proteins. In mammalian cells, mitochondrial fusion is regulated by mitofusin-1 and -2 (MFN-1/2) and optic atrophy 1 (OPA1), whereas mitochondrial fission is controlled by dynamin-1-related protein, Drp1 (Chan, 2006a;Scott and Youle, 2010) and its mitochondrial adaptors such as Fis1, Mff and MIEF1 (Otera et al, 2010;Palmer et al, 2011;Zhao et al, 2011).…”