4.7 Review

The lysosome as an imperative regulator of autophagy and cell death

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 23, Pages 7435-7449

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03988-3

Keywords

Lysosome; Autolysosome; Autophagic lysosome reformation; Autophagy; Autophagic cell death

Funding

  1. Government of India, Ministry of Science & Technology, Department of Science and Technology [DST/INSPIRE Fellowship/2017/IF170344]
  2. Science and Engineering Research Board (SERB), Department of Science and Technology [EMR/2016/001246]

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Lysosomes are crucial organelles responsible for degrading cellular cargo and maintaining cellular homeostasis, playing a critical role in the connection between autophagy and endocytosis. Damage to the lysosomal membrane can lead to selective lysosomal degradation pathway and trigger lysophagy in severe cases.
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. [GRAPHICS] .

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