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J Mol Cell Cardiol. 2021 Dec 14;165:1-8. doi: 10.1016/j.yjmcc.2021.12.006. Epub 2021 Dec 14.

The role of autophagy in death of cardiomyocytes.

Journal of molecular and cellular cardiology

Shohei Ikeda, Daniela Zablocki, Junichi Sadoshima

Affiliations

  1. Department of Cardiovascular Medicine, International University of Health and Welfare Hospital, Tochigi, Japan; Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.
  2. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.
  3. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA. Electronic address: [email protected].

PMID: 34919896 DOI: 10.1016/j.yjmcc.2021.12.006

Abstract

Autophagy mediates cellular quality control mechanisms and energy homeostasis through lysosomal degradation. Autophagy is typically viewed as an adaptive process that allows cells to survive against stress, such as nutrient deprivation and hypoxia. However, autophagy also mediates cell death during development and in response to stress. Cell death accompanied by autophagy activation and accumulation of autophagosomes has been classified as type II programmed cell death. Compared to the wealth of knowledge regarding the adaptive role of autophagy, however, the molecular mechanisms through which autophagy induces cell death and its functional significance are poorly understood. Autophagy is activated excessively under some conditions, causing uncontrolled degradation of cellular materials and cell death. An imbalance between autophagosome formation and lysosomal degradation causes a massive accumulation of autophagosomes, which subsequently causes cellular dysfunction and death. Dysregulation of autophagy induces a unique form of cell death, termed autosis, with defined morphological and biochemical features distinct from other forms of programmed cell death, such as apoptosis and necrosis. In the heart, dysregulated autophagy induces death of cardiomyocytes and actively mediates cardiac injury and dysfunction in some conditions, including reperfusion injury, doxorubicin cardiomyopathy, and lysosomal storage disorders. The goal in this review is to introduce the concept of autophagic cell death and discuss its functional significance in various cardiac conditions.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: Autophagy; Autosis; Cardiac glycosides; Cardiomyocytes; Cell death

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