Autophagy is a conserved lysosome-mediated degradative pathway required for cell survival, homeostasis and human health. Autophagy is carried out by membranes called autophagosomes which capture cytosolic cargo such as damaged mitochondria and deliver it to lysosomes. Autophagosome formation is a complex process that requires a cohort of autophagy proteins (ATG proteins) acting in a coordinated manner. This core machinery drives the formation of the phagophore, the nucleating membrane, and the nascent autophagosome. Under amino acid starvation this coordinated response is initiated by the transmembrane protein ATG9 and the serine/threonine ULK1/2 kinase. ATG9 trafficking and ULK1/2 activation sense signals which drive the initiation of the phagophore. Following initiation, the Class III PI3 kinase, and the PI3P effector WIPI2 mediate recruitment of ATG12-5-16L1, and the ATG8 family of proteins. ATG8s are required for cargo selection and maturation of the autophagosome. In an effort to understand the formation and maturation of autophagosomes we are studying the trafficking and function of ATG9, substrates of the ULK1/2 complex, and the selectivity of the ATG8 proteins. Our recent results will be presented which provide new insight into these processes.
This work was supported by the Francis Crick Institute (FC001187) which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.