Regulation of membrane trafficking during glucose starvation

Membrane traffic is a fundamental biological process that allows cells to respond to and adapt to their environments by rapidly altering cell surface composition. We recently reported that during glucose starvation the budding yeast Saccharomyes cerevisiae internalizes many cell surface proteins and routes
these to the lysosome/vacuole for degradation. This process, and not canonical macro‐autophagy, seems to be required for cell survival during glucose starvation. Because the selection of proteins for internalization appears to be a relatively non‐specific process, we hypothesized alternative endocytic or
internal trafficking pathways might mediate glucose starvation induced degradation. To probe the mechanistic requirements for glucose starvation induced degradation, we performed candidate and genome wide screens. We found that the degradation of proteins upon glucose starvation requires many components of the canonical degradative machinery used under normal conditions: such as ubiquitination, clathrin, HOPS components, and SNARE proteins. However, we also found an unexpected phenotype for genes involved in mitochondrial function. We observed many genes required for oxidative phosphorylation led to the accumulation of endocytosed cargo in compartments similar to those seen in late endocytic mutants such as the ESCRT complex. This suggests that under acute energy stress, yeast can mount sufficient energy reserves to perform the internalization step of endocytosis, however there is insufficient energy to mediate late steps in delivery to the lysosome. These finding may explain the link between mitochondrial dysfunction and lysosomal storage disorders.