Title:
Mitochondrial dynamics: GTPases regulating mitochondrial fusion and fission

Naotada Ishihara
Department of Protein Biochemistry, Institute of Life Science, Kurume University

Abstract:
Mitochondrial morphology is dynamic in response to cell signaling and differentiation by regulating their fusion and fission. Mitochondrial fusion plays important role in maintenance of active mitochondria, and the mitochondrial fusion regulating GTPase proteins Mitofusin 2 and OPA1 were identified as the cause gene products for neurodegenerative disorders. Dynamin-related GTPase protein Drp1 is essential factor for regulating mitochondrial fission. When we analyzed roles of mitochondrial fission using Drp1-deficient mice and cells, we found that Drp1 is dispensable for cell growth and maintenance of active mitochondria in cultured fibroblasts. However, mice lacking Drp1 were embryonic lethal, exhibiting developmental abnormalities, particularly in the forebrain. Neural cell-specific Drp1-deficient mice died shortly after birth due to brain hypoplasia with apoptosis. These defects highlight the importance of mitochondrial dynamics within morphologically and functionally differentiated cells, such as highly polarized neurons.

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