Regulation of mitochondrial fission and fusion in neuronal injury

Arezu Jahani-Asl, Université D'Ottawa / University Of Ottawa, Université D'Ottawa / University Of Ottawa
Mitochondria are dynamic organelles meaning that they constantly fuse with each other, divide and move. The creation of such dynamic nature of mitochondria seems to be very purposeful. For example mitochondrial fusion is identified as a repair mechanism to dilate damaged mitochondria while mitochondrial fission results in the mitochondrial biogenesis and generates smaller mass mitochondria that can move faster to strategic locations within cellular compartments. In mammals, Mitofusin 2 (Mfn2)
more » ... outer mitochondrial membranes (OMM) protein and Optic atrophy 1 (Opal), found in the inter mitochondrial space in association with the inner mitochondrial membrane (IMM), regulate OMM and IMM fusion, respectively. In non neuronal cells, the key components of mitochondrial dynamics have been linked to the regulation of cell death induced by apoptotic signaling. Neurons possess unique morphological complexities and undergo cell death by distinct mechanisms which are far more complicated than just apoptosis. A fundamental question that has arisen from the previous studies is whether mitochondrial fission and fusion machineries impact neuronal survival and function. The first goal of my PhD thesis has been to tackle the important questions of whether mitochondrial morphology defects are associated with neuronal demise and whether components of mitochondrial fusion can rescue neuronal loss in physiologically relevant models. The results of my studies have culminated in a number of key findings. First, mitochondrial morphological defects have been identified as early events following different modes of neuronal injury such as DNA damage (induced by camptothecin), oxidative stress (induced by H2O2) and calcium toxicity (induced by overactivation of glutamate receptors). While mitochondrial fission contributes to the dramatic mitochondrial fragmentation following neuronal death, a defective mitochondrial fusion and loss of IMM integrity are identified as two of the major mechanisms contributing to the mitochondrial dysfunction an [...]
doi:10.20381/ruor-19979 fatcat:ylelow6dxzetrkfstyg3j3uhtq