Non-apoptotic mitochondrial functions of C. elegans CED-9 BCL2

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BCL2-like proteins are crucial regulators of programmed cell death type I, also referred to as apoptosis, in animals as diverse as the nematode Caenorhabditis elegans and mammals. Recently, it has been suggested that BCL2-like proteins also have non-apoptotic functions. For example, BCL2-like proteins have been implicated in a process referred to as mitochondrial dynamics. Mitochondrial dynamics describes the fact that the mitochondrial network within a cell frequently undergoes cycles of fusion and fission and can change its overall morphology in response to specific signals. While mitochondrial dynamics is critical for cellular function, the specific physiological roles of mitochondrial dynamics remain to be elucidated. We have demonstrated that the BCL2-like protein CED-9 of C. elegans can promote both mitochondrial fusion and mitochondrial fission. Furthermore, we found that CED-9 does so by directly interacting with the dynamin-related GTPases FZO-1 Mfn and DRP-1 Drp1, which are required for mitochondrial fusion and fission, respectively. The goal of the proposed studies is to test the model that in healthy, non-apoptotic cells, CED-9 acts as a coupler of mitochondrial fusion and mitochondrial fission during cycles of fusion and fission. To that end, we will use a combination of cell biological, genetic and biochemical approaches. Results from the proposed studies will not only improve our understanding of the non-apoptotic functions of BCL2-like proteins but help to determine the physiological roles of mitochondrial dynamics.