Global analysis of fission yeast mating genes reveals new autophagy factors.
Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in animal development and human diseases. Molecular understanding of autophagy has mainly come from the budding yeast Saccharomyces cerevisiae, and it remains unclear to what extent the mechanisms are the same in other organisms. Here, through screening the mating phenotype of a genome-wide deletion collection of the fission yeast Schizosaccharomyces pombe, we obtained a comprehensive catalog of autophagy genes in this highly tractable organism, including genes encoding three heretofore unidentified core Atg proteins, Atg10, Atg14, and Atg16, and two novel factors, Ctl1 and Fsc1. We systematically examined the subcellular localization of fission yeast autophagy factors for the first time and characterized the phenotypes of their mutants, thereby uncovering both similarities and differences between the two yeasts. Unlike budding yeast, all three Atg18/WIPI proteins in fission yeast are essential for autophagy, and we found that they play different roles, with Atg18a uniquely required for the targeting of the Atg12-Atg5·Atg16 complex. Our investigation of the two novel factors revealed unforeseen autophagy mechanisms. The choline transporter-like protein Ctl1 interacts with Atg9 and is required for autophagosome formation. The fasciclin domain protein Fsc1 localizes to the vacuole membrane and is required for autophagosome-vacuole fusion but not other vacuolar fusion events. Our study sheds new light on the evolutionary diversity of the autophagy machinery and establishes the fission yeast as a useful model for dissecting the mechanisms of autophagy.
National Institute of Biological Sciences, Beijing, China.
Ling-Ling
LL
Sun
Ming
M
Li
Fang
F
Suo
Xiao-Man
XM
Liu
En-Zhi
EZ
Shen
Bing
B
Yang
Meng-Qiu
MQ
Dong
Wan-Zhong
WZ
He
Li-Lin
LL
Du
D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D016681:Genome, Fungal; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010455:Peptides / Q000235:genetics*; D010588:Phagosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014617:Vacuoles
C441008:ATG18 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D004268:DNA-Binding Proteins; C089516:Mating Factor, S pombe; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins