Post-Golgi Sec Proteins Are Required for Autophagy in Saccharomyces cerevisiae

Abstract

Macroautophagy is linked to various diseases in humans, including cancer and neurodegeneration. The morphological hallmark is the formation of the double-membrane autophagosome, which is the most complex aspect of macroautophagy. We demonstrate a role for post-Golgi Sec proteins, Sec2 and Sec4, in autophagosome formation.

Abstract

In eukaryotic cells, autophagy mediates the degradation of cytosolic contents in response to environmental change. Genetic analyses in fungi have identified over 30 autophagy-related ( ATG) genes and provide substantial insight into the molecular mechanism of this process. However, one essential issue that has not been resolved is the origin of the lipids that form the autophagosome, the sequestering vesicle that is critical for autophagy. Here, we report that two post-Golgi proteins, Sec2 and Sec4, are required for autophagy. Sec4 is a Rab family GTPase, and Sec2 is its guanine nucleotide exchange factor. In sec2 and sec4 conditional mutant yeast, the anterograde movement of Atg9, a proposed membrane carrier, is impaired during starvation conditions. Similarly, in the sec2 mutant, Atg8 is inefficiently recruited to the phagophore assembly site, which is involved in autophagosome biogenesis, resulting in the generation of fewer autophagosomes. We propose that following autophagy induction the function of Sec2 and Sec4 are diverted to direct membrane flow to autophagosome formation.