Biology Seminar - Richard Youle | Wednesday, February 15th, 2023 - 4 pm

Biology Seminar

February 15th, 2023 - 4 pm

Reception -3:30 pm

Chen 100

Richard Youle

Senior Investigator Biochemistry Section, Surgical Neurology Branch National Institute of Neurological Disorders and Stroke

Title: Autophagy, Innate Immunity and Parkinson's Disease

Abstract:

PINK1 and Parkin, both mutated in familial PD, work intimately together to initiate autophagy of impaired mitochondria. Absence of Parkin in Drosophila causes muscle degeneration that is rescued by loss of STING, an innate immune activator of NFkB in flies and interferon in man. STING responds to cyclic dinucleotides produced by cGAS upon binding cytosolic dsDNA. Mitochondria, if impaired, may release mtDNA that activates STING signaling suggesting that loss of Parkin and loss of quality control mitophagy may also allow mtDNA release and activation of STING. Human studies on loss of PINK1 and Parkin are consistent with this model. STING activation not only activates interferon induction in human cells, it activates the lipidation of LC3, a canonical marker of autophagy. However, the mechanism and consequences of STING activation of LC3 lipidation are distinct from starvation induced autophagy. The outcome of STING-induced lipidation of LC3 yields potential new insights into mitophagy and innate immune mechanisms.