Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Cells. 2022 Jul 22;11(15):2262. doi: 10.3390/cells11152262.

Abstract

Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells. However, under stress conditions, such as a lack of nutrients or trophic factors, it works as a survival mechanism that allows the generation of metabolic precursors for the proper functioning of the cells until the nutrients are available. Neurons, as post-mitotic cells, depend largely on autophagy to maintain cell homeostasis to get rid of damaged and/or old organelles and misfolded or aggregated proteins. Therefore, the dysfunction of this process contributes to the pathologies of many human diseases. Furthermore, autophagy is highly active during differentiation and development. In this review, we describe the current knowledge of the different pathways, molecular mechanisms, factors that induce it, and the regulation of mammalian autophagy. We also discuss its relevant role in development and disease. Finally, here we summarize several investigations demonstrating that autophagic abnormalities have been considered the underlying reasons for many human diseases, including liver disease, cardiovascular, cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, cancers, and, more recently, infectious diseases, such as SARS-CoV-2 caused COVID-19 disease.

Keywords: autophagy; development; diseases; modulators; molecular mechanisms; morphogenesis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology
  • COVID-19*
  • Homeostasis
  • Humans
  • Lysosomes / metabolism
  • Mammals
  • SARS-CoV-2

Grants and funding

This work was founded by the program PAPIIT/DGAPA/UNAM, grant numbers: IA210620, IA208118 and IA202021, and by the Mexican Research Councyl (CONACYT), “Ciencia Básica y/o Ciencia de Frontera Modalidad: Paradigmas y Controversias de la Ciencia 2022” grant numbers 319578 and 319433. And by Fondo Nacional de Ciencia, Tecnología del Ministerio de Educación Superior Ciencia y Tecnología. República Dominicana 2018-2019-2A3-208 granted to J.-L.M. and M.P.-H.