Atg15 in Saccharomyces cerevisiae consists of two functionally distinct domains

Abstract

Autophagy is a cellular degradation system widely conserved among eukaryotes. During autophagy, cytoplasmic materials fated for degradation are compartmentalized in double membrane–bound organelles called autophagosomes. After fusing with the vacuole, their inner membrane–bound structures are released into the vacuolar lumen to become autophagic bodies and eventually degraded by vacuolar hydrolases. Atg15 is a lipase essential for disintegration of autophagic body membranes and has a transmembrane domain at the N-terminus and a lipase domain at the C-terminus. However, the roles of both domains in vivo are not well understood. In this study, we found that the N-terminal domain alone can travel to the vacuole via the multivesicular body pathway, and that targeting of the C-terminal lipase domain to the vacuole is required for degradation of autophagic bodies. Moreover, we found that the C-terminal domain could disintegrate autophagic bodies when it was transported to the vacuole via the Pho8 pathway instead of the multivesicular body pathway. Finally, we identified H435 as one of the residues composing the putative catalytic triad, and W466 as an important residue for degradation of autophagic bodies. This study may provide a clue to understanding how the C-terminal lipase domain recognizes autophagic bodies to degrade them. [Media: see text] [Media: see text]

Chemoproteomic profiling of serine hydrolases reveals the dynamic role of lipases inPhaeodactylum tricornutum

“…Notably, two genes (Phatr3_J43856, Phatr3_J44028) were highly expressed under N-starvation, suggesting their involvement in TAG turnover for energy and carbon homeostasis under this condition. In line with this premise, Phatr3_J43856, is annotated as a gene for the autophagy- related lipase ATG15, involved in vacuolar breakdown of autophagic body membrane and TAG breakdown (lipophagy) in yeast (Hirata et al, 2021). Further study on the role of this lipase in P. tricornutum is needed.…”

Vacuolar Processing Enzymes in Plant Programmed Cell Death and Autophagy

“…Therefore, homology studies may help to fill the gaps in knowledge about the molecular mechanisms of plant autophagy [ 11 ]. In yeast, the degradation of autophagic bodies is processed by the following enzymes: proteinase B (Prb1), proteinase A (Pep4) [ 11 , 99 ], and Atg15 possessing lipolytic activity [ 11 , 100 , 101 ]. Additionally, Atg42/Ybr139w and its homolog carboxypeptidase Y (Prc1) are likely also involved in the degradation of autophagic bodies in yeast [ 11 , 102 ].…”

Metabolic Dysfunction in Motor Neuron Disease: Shedding Light through the Lens of Autophagy

“…Lipase. Involved in autophagic body disintegration (in Saccharomyces cerevisiae) [50] As a process critical for maintaining intracellular homeostasis, autophagy is fundamentally linked to cellular energy metabolism.…”