Molecular Mechanisms of Autophagy and Membranes Dynamics

Autophagy is a vital catabolic mechanism employed by cells to maintain nutrient homeostasis and organellar quality control. Our main interest is to characterize the molecular mechanisms responsible for endoplasmic reticulum (ER) dynamics during autophagy induction. The ER is a continuous system of membrane sheets, tubules and matrices, which constantly reshape to fulfil physiological functions like: calcium homeostasis, protein quality control and secretion. An important aspect is the restoration of the original pre-stress ER network, which requires the disassembly and elimination of excess or damaged ER parts. ER membranes are rapidly remodeled by selective autophagy, ER-phagy, which is regulated by a subset of specific receptors. Studying the mechanisms of ER remodeling during autophagy is not only important for acquiring new information on a fundamental cellular process but also bares major medical implications and therapeutic potential. ER-phagy plays a prominent role in the fight against viral and bacterial infections. Indeed, ER-phagy-related receptors have been associated with several types of cancers. Moreover, mutations in ER resident proteins are responsible for hereditary sensory and autonomic neuropathies (HSAN). The aim of our research is to investigate the involvement of the known autophagy pathways in ER remodeling; to characterize new ER-phagy receptors and their role in membrane dynamics, and to unravel the molecular mechanisms of ER-related axonal disorders. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.