Figure 3. Mitochondrial fission.

(a) Drp1 is found in the cytoplasm, but cycles on and off mitochondria, possibly by indirect interaction with the outer-membrane associated hFis1. Once bound to the mitochondrial outer membrane, Drp1 forms large clusters or foci, which mediate membrane fission. OM indicates the outer membrane and IM indicates the inner membrane. (b) Domain model of Drp1 (Swissprot: O00429) showing the conserved GTPase domain, helical domain, and GTP effector domain (GED). (c) Fluorescent 3D microscopic image of a fused, elongated mitochondrion (red) in a healthy neuron and round, fissioned mitochondria in a neuron exposed to nitrosative stress. The mitochondrial labeling results from DsRed-Mito expression.(d) Slice through an EM tomographic volume showing four fragmented mitochondria (indicated by arrows) in a neuronal process after exposure to an NO donor, which triggers mitochondrial fission. Mitochondria are recognizable because of their cristae structure, even with some cristae membrane degradation. (e) Top view of the surface-rendered volume after segmentation of the same four mitochondria as shown in (d). The outer membrane is shown in pale blue and the cristae in various colors. Cristae fragmentation is evident from the smaller and regionally confined cristae. (f) Side view of the surface-rendered volume. The outer membrane is made transparent to better visualize the cristae. Fission induces a profound remodeling of the inner membrane with cristae vesiculation.