Phagophore-lysosome/vacuole fusion in mutant yeast and mammalian cells

Autophagy. 2023 Sep;19(9):2595-2600. doi: 10.1080/15548627.2023.2205272. Epub 2023 Apr 28.

Abstract

Macroautophagy/autophagy is a process through which the phagophores engulf non-essential or damaged cellular materials, forming double-membrane autophagosomes (APs) and fusing with lysosomes/vacuoles, after which the materials are degraded for recycling purposes. Autophagy is associated with increased cell survival under different stress conditions. AP-lysosome/vacuole fusion is a critical step in autophagy. Some mutant cells can accumulate phagophores under autophagy-induction conditions. Autophagy is interrupted when accumulated phagophores cannot fuse with lysosomes/vacuoles, resulting in a significant decrease in cell survivability. However, phagophore-lysosome/vacuole fusion has been reported in related mammalian cells and yeast mutant cells. This observation indicates that it is possible to restore a partial autophagy process after interruption. Furthermore, these findings indicate that phagophore closure is not a prerequisite for its fusion with the lysosome/vacuole in the mutant cells. The phagophore-lysosome/vacuole fusion strategy can significantly rescue defective autophagy due to failed phagophore closure. This commentary discusses the fusion of phagophores and lysosomes/vacuoles and implications of such fusion events.Abbreviations: AB: autophagic body; AL: autolysosome; AP: autophagosome; ATG: autophagy related; EM: electron microscopy; ESCRT: endosomal sorting complex required for transport; ET: electron tomography; FIB: focus ion beam; IM: inner membrane; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; OM; outer membrane; STX17: syntaxin 17; TEM: transmission electron microscopy; TM: transmembrane domain; Vps: vacuolar protein sorting; WT: wild-type.

Keywords: Autolysosome; autophagic body; inner membrane of phagophore or autophagosome; outer membrane of phagophore or autophagosome; phagophore; phagophore-lysosome/vacuole fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes* / metabolism
  • Autophagy / genetics
  • Lysosomes / metabolism
  • Mammals
  • Membrane Fusion
  • Saccharomyces cerevisiae / genetics
  • Vacuoles* / metabolism

Grants and funding

This study was supported by the Natural Science Foundation of China [91954125, 31871428, and 31671479].