Mitochondrial stress signaling in disease and aging (474.3)

Abstract

Mitochondria are multi‐faceted organelles in eukaryotic cells that stand at the nexus of energy metabolism, oxidative stress, and apoptosis. Consequently, circumstances (genetics, environmental factors, aging) that result in mitochondrial dysfunction disrupt a multitude of cellular processes that can cause human disease pathology, ranging from heart, skeletal muscle and nerve dysfunction to diabetes, blindness, and deafness. Of course, a major function of mitochondria is to generate ATP through the process of oxidative phosphorylation (OXPHOS), which also produces reactive oxygen species (ROS). Oxidative stress due to increased production of mitochondria‐derived ROS, declines in cellular energy metabolism, and disruption of apoptotic responses are some of the major downstream cellular consequences leading to the observed pathology of mitochondrial‐based diseases. In addition to causing molecular damage, ROS also participate in numerous signaling pathways that regulate diverse physiological processes, including stress resistance, cell differentiation, proliferation, and apoptosis. In my talk, I will highlight recent studies from my laboratory that link mitochondrial ROS and stress signaling to disease pathology and regulation of lifespan.