Noboru Mizushima, MD, PhD
Photo: Noboru Mizushima



Elected 2006
Studies in my laboratory focus on autophagy, a dynamic degradation system within cells. Eukaryotes have two major protein degradation systems: one is the ubiquitin-proteasome system that accounts for the selective degradation of most short-lived proteins, and the other one is the lysosomal system. Autophagy is the primary means for the degradation of cytoplasmic constituents in the lysosome. We have dissected the autophagic process in mammalian cells and proposed a model in which autophagosome is generated by elongation of a small vesicle in a manner dependent on two ubiquitin-like proteins, Atg12 and LC3. We also study the physiological role of autophagy using an autophagy-indicator mouse model (GFP-LC3 mice) and autophagy gene-KO mice. We have shown that autophagy is upregulated following food withdrawal and during early neonatal starvation period in mice and proposed that increased intracellular generation of amino acids by autophagy is a physiologically important starvation response. Additionally, we showed that basal autophagy has a critical role in intracellular protein quality control under normal conditions, particularly in neurons, which is independent of the role of induced autophagy as an adaptation to starvation. We are now examining additional roles of autophagy in mammals and exploring molecular mechanism of autophagy regulation.