The lysosome as an imperative regulator of autophagy and cell death

Cell Mol Life Sci. 2021 Dec;78(23):7435-7449. doi: 10.1007/s00018-021-03988-3. Epub 2021 Oct 30.

Abstract

Lysosomes are single membrane-bound organelles containing acid hydrolases responsible for the degradation of cellular cargo and maintenance of cellular homeostasis. Lysosomes could originate from pre-existing endolysosomes or autolysosomes, acting as a critical juncture between autophagy and endocytosis. Stress that triggers lysosomal membrane permeabilization can be altered by ESCRT complexes; however, irreparable damage to the membrane results in the induction of a selective lysosomal degradation pathway, specifically lysophagy. Lysosomes play an indispensable role in different types of autophagy, including microautophagy, macroautophagy, and chaperone-mediated autophagy, and various cell death pathways such as lysosomal cell death, apoptotic cell death, and autophagic cell death. In this review, we discuss lysosomal reformation, maintenance, and degradation pathways following the involvement of the lysosome in autophagy and cell death, which are related to several pathophysiological conditions observed in humans.

Keywords: Autolysosome; Autophagic cell death; Autophagic lysosome reformation; Autophagy; Lysosome.

Publication types

  • Review

MeSH terms

  • Aging / pathology
  • Animals
  • Apoptosis / immunology*
  • Autophagy / immunology*
  • Cell Membrane / metabolism
  • Endocytosis / immunology*
  • Humans
  • Intracellular Membranes / metabolism
  • Lysosomes / immunology*