INVOLVEMENT OF MITOCHONDRIAL PROTEINS IN AUTOPHAGY: A POSSIBLE LINK WITH MITOCHONDRIAL DISORDERS

Mitochondria originated as bacteria that have been engulfed by primitive eukaryotic cells. Mitochondria are membrane enclosed organelles found in most eukaryotic cells and they are considered the cell’s powerhouse. Indeed they use the food we eat to generate most of the cell's supply of ATP which is used as a source of energy. Mitochondria have their own independent genome, the material of which is known as mitochondrial DNA (mtDNA). Mutations in mitochondrial genes can lead to a number of mitochondrial disorders. Mutations in mtDNA are common because the error checking mechanisms present during nuclear DNA replication are absent. Mitochondria are emerging as a key player in a cell death process that is attracting a great interest in the scientific community: the autophagy. Autophagy, or autophagocytosis (derived from Greek roots: auto-self, and phagy-eating), is a catabolic process involving the degradation of a cell's own long-lived components. Autophagy is a part of everyday normal cell growth and development and in particular the selective autophagy of mitochondria, termed "mitophagy" may play a key role in accumulation of somatic mutations of mtDNA. The proposed research investigates the involvement of mitochondrial proteins in dysregulation of autophagy process and the correlation with human genetics mitochondrial disorders. Finally the project will study how the calcium signaling, the most important intracellular second messenger that governs countless cellular functions, already known to be involved in mitochondrial disease, may affect autophagy.