The endosomal sorting complex required for transport (ESCRT) is a multi protein complex consisting of five subunits, ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III and the AAA ATPase VPS4. In eukaryotic cells, this protein complex is required for the degradation of ubiquitinylated membrane proteins by forming intraluminal vesicles in the lumen of multivesicular bodies, which fuse with lysosomes for degradation. ESCRT proteins are involved in the last steps of cytokinesis, the abscission of the midbody, and in budding of enveloped retroviruses out of cells. Thereby this selective membrane protein degradation pathway is involved in tumorigenesis. Here we could show that the ESCRT-III subunit CHMP3 is required for cell growth and survival. Upon shRNA mediated knockdown of CHMP3, cells stop to grow. In addition CHMP3 is required for better survival under nutrient limitation, and the MVB pathway helps to suppress basal autophagy. Already under basal conditions, we could observe that CHMP3 knockdown cells upregulate autophagy. Amino acid starvation has a dramatic effects on the survival of CHMP3 knockdown cells. The number of viable CHMP3 knockdown cells declines under nutrient limitation. Their numbers reduce under this conditions much faster than wildtypes. We observed, that cell death is upregulated with ongoing starvation in CHMP3 knockdown cells within 24h. Importantly, experiments suggest that the MVB pathway is not required for the formation of autophagosomes, and their delivery to the lysosome.
Taken together, we could show that selective membrane protein degradation via the MVB pathway is essential for mammalian cell growth and survival under starvation conditions.