Centrosome to autophagosome signaling: Specific GABARAP regulation by centriolar satellites

Abstract

Yeast have one Atg8 protein; however, multiple Atg8 orthologs (LC3s and GABARAPs) are found in humans. We discovered that a population of the Atg8 ortholog GABARAP resides on the centrosome and the peri-centrosomal region. This centrosomal pool of GABARAP translocates to forming autophagosomes upon starvation to activate autophagosome formation in a non-hierarchical pathway. How this centrosome-to-phagophore delivery of GABARAP occurs was not understood. To address this, we have shown that the archetypal centriolar satellite protein PCM1 regulates recruitment of GABARAP to the centrosome. PCM1 recruits GABARAP, but not MAP1LC3B, directly to centriolar satellites through a LC3-interacting region (LIR) motif. Furthermore, PCM1, in concert with its interacting centriolar satellite E3 ligase MIB1, controls GABARAP stability, K48-linked ubiquitination and GABARAP-mediated autophagic flux.