MITOCHONDRIAL FISSION AND NEURODEGENERATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims: Mitochondria are pivotal for neuronal energy supply to support vital functions e.g. ion pump and channel activity, synaptic transmission, and axonal/dendritic transport. Deficits in mitochondrial function inevitably result in neuronal dysfunction or cell death. Moreover, there is increasing evidence that mitochondrial dysfunction underlies several neurodegenerative disorders. Less clear, however, is what exactly causes these mitochondrial injuries. Mitochondria are dynamic organelles undergoing fusion and fission. Mitochondrial fission and fusion has to be balanced for normal neuronal function and is orchestrated by large dynamin-related GTPases that exert opposing effects e.g. Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, while Mitofusin 1 and Mitofusin 2 (Mfn1, 2) of OPA1 is required for mitochondrial fusion. Hereditary loss-of-function mutations in Mfn 2 or OPA1 cause neurodegenerative disorders in humans.