Article

Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1.

Institute of Biotechnology and Department of Life Sciences, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Annals of the New York Academy of Sciences (impact factor: 3.15). 07/2010; 1201:34-9. DOI:10.1111/j.1749-6632.2010.05629.x pp.34-9
Source: PubMed

ABSTRACT 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.

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Keywords

conformational change
 
covalent modification
 
Drp1 modifications
 
dynamic nature
 
dynamin-related GTPase undergoes
 
fusion events
 
mammalian Drp1 protein
 
membrane deformation
 
Mfn2
 
mitochondrial division
 
mitochondrial fission
 
mitochondrial fission protein Drp1
 
mitochondrial membrane dynamics
 
mitochondrial outer membrane
 
modifications
 
normal regulation
 
posttranslational modifications
 
proteins
 
regulatory mechanisms
 
Shifts
 

Chuang-Rung Chang