The importance of mitochondrial fusion for embryogenesis was shown with Mfn1 and Mfn2 knock-out mice, which die in utero at midgestation because of a placental deficiency, whereas the Mfn1 Mfn2 double knockout mice die even earlier in development ( 4). It has been less clear why mitochondrial fission and fusion are also needed for nonproliferating cells, but the importance of these processes is evident from nonproliferating neurons, which cannot survive without mitochondrial fission, and from two human diseases, dominant optic atrophy and Charcot Marie Tooth disease type 2A, which are caused by fusion defects. Mitochondrial fission is essential for growing and dividing cells to populate them with adequate numbers of mitochondria. Mitochondrial fission and fusion machineries are regulated by proteolysis and posttranslational modifications ( 1). Fusion between mitochondrial outer membranes is mediated by membrane-anchored dynamin family members named Mfn1 and Mfn2 in mammals, whereas fusion between mitochondrial inner membranes is mediated by a single dynamin family member called Opa1 in mammals. Mdv1 recruits Dnm1 to mitochondrial fission sites in yeast, whereas Mid49, Mid51, and Mff recruit Drp1 to mitochondria in mammals ( 2), often at sites where mitochondria make contact with the endoplasmic reticulum ( 3).

Yeast share with mammals this core function of Drp1 but have distinct accessory proteins. Drp1 is recruited from the cytosol to form spirals around mitochondria that constrict to sever both inner and outer membranes. The mitochondrial inner membrane, which encloses the matrix, is folded into cristae that contain membrane-bound oxidative phosphorylation enzyme complexes and the bulk of the soluble electron transport proteins such as cytochrome c, whereas the smooth mitochondrial outer membrane encapsulates the inner membrane and an intermembrane space.ДЇission is mediated by a cytosolic dynamin family member (Drp1 in worms, flies, and mammals and Dnm1 in yeast). Their combined actions divide and fuse the two lipid bilayers that surround mitochondria. Mitochondrial fission and fusion processes are both mediated by large guanosine triphosphatases (GTPases) in the dynamin family that are well conserved between yeast, flies, and mammals ( 1). Mitochondrial Fusion and Fission Proteins Here, we discuss how fission and fusion contribute to mitochondrial quality control and the responses of mammalian cells to stress. The wide range of mitochondrial lengths observed in different cell types and under different conditions results from changes in the balance between the rates of mitochondrial fission and fusion. Rapid fission and fusion of mitochondria in cultured fibroblasts allows for the complete redistribution of mitochondrial green fluorescent protein (GFP) from one mitochondrion to all the other mitochondria of a cell within an hour.

Their shapes change continually through the combined actions of fission, fusion, and motility. When mitochondria are viewed in live cells, it becomes immediately apparent that their morphologies are far from static. Fibroblast mitochondria, for example, are usually long filaments (1 to 10 Ојm in length with a fairly constant diameter of ~700 nm), whereas hepatocyte mitochondria are more uniformly spheres or ovoids. Mitochondrial morphologies vary widely among different cell types. Mitochondria are double-membraneвЂ“bound subcellular organelles that provide a host of metabolic functions, including energy production through oxidative phosphorylation.

Spontaneous fission