Investigating the relationship between mitochondrial dysfunction and apoptosis, autophagy and cellular senescence

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In addition to energy production, the mitochondria play a crucial role in apoptosis, autophagy and senescence. The relationship/crosstalk between redox signaling, autophagy, senescence and mitochondrial dysfunction is not well understood. It is hypothesized that accumulation of toxic proteins (oxidized or nitrosylated) and malfunctioning of mitochondrion lead to further oxidative stress that could lead to any of the aforementioned phenomena. Autophagy is induced in response to such stress in order to eliminate dysfunctional proteins and organelles. However, if autophagy is inhibited, cell death (in the neuronal system) or senescence (in fibroblasts) is activated. Using normal human fibroblasts with wild type and Presenilin-1 mutations as models, the research program is set to investigate the mechanism of cellular switches that trigger senescence, apoptosis and autophagy and role of mitochondria in these processes.