Mitochondria in cells comprise a tubulovesicular network shaped continuously by 
complementary fission and fusion events. The mammalian Drp1 protein plays a key 
role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in 
the balance between these opposing processes can occur rapidly, indicating that 
modifications to these proteins may regulate mitochondrial membrane dynamics. We 
highlight posttranslational modifications of the mitochondrial fission protein 
Drp1, for which these regulatory mechanisms are best characterized. This 
dynamin-related GTPase undergoes a number of steps to mediate mitochondrial 
fission, including translocation from cytoplasm to the mitochondrial outer 
membrane, higher-order assembly into spirals, GTP hydrolysis associated with a 
conformational change and membrane deformation, and ultimately disassembly. Many 
of these steps may be influenced by covalent modification of Drp1. We discuss 
the dynamic nature of Drp1 modifications and how they contribute not only to the 
normal regulation of mitochondrial division, but also to neuropathologic 
processes.