Fig. 1. Mitochondrial fusion and fission dissected. (A) Fusion of mitochondria requires the sequential interaction of outer and inner membranes. Fusion of the outer membranes of two adjacent mitochondria requires low GTP levels, whereas the subsequent fusion of the inner membranes requires high GTP levels. Two components of the mitochondrial fusion machinery are known in mammalian cells, the outer membrane proteins mitofusins Mfn1 and Mfn2, which each have a cytosolic GTPase domain and two coiled-coil regions, and the intermembrane space proteins GTPase OPA1. (B) Models and molecules of mitochondrial fission. Fission protein 1 (Fis1) is localized uniformly to the mitochondrial outer membrane, whereas dynamin-related protein (Drp1) is localized to the cytosol and punctate spots on mitochondria. Some of these spots are constriction sites that lead to mitochondrial fission. How Drp1 is recruited to mitochondria is unclear.