Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Int J Mol Sci. 2021 Nov 18;22(22):12466. doi: 10.3390/ijms222212466.

Abstract

Research in biomedical sciences has changed dramatically over the past fifty years. There is no doubt that the discovery of apoptosis and autophagy as two highly synchronized and regulated mechanisms in cellular homeostasis are among the most important discoveries in these decades. Along with the advancement in molecular biology, identifying the genetic players in apoptosis and autophagy has shed light on our understanding of their function in physiological and pathological conditions. In this review, we first describe the history of key discoveries in apoptosis with a molecular insight and continue with apoptosis pathways and their regulation. We touch upon the role of apoptosis in human health and its malfunction in several diseases. We discuss the path to the morphological and molecular discovery of autophagy. Moreover, we dive deep into the precise regulation of autophagy and recent findings from basic research to clinical applications of autophagy modulation in human health and illnesses and the available therapies for many diseases caused by impaired autophagy. We conclude with the exciting crosstalk between apoptosis and autophagy, from the early discoveries to recent findings.

Keywords: Apaf1; Bcl-2; C. elegans; apoptosis; autophagy; caspase; electron microscopy.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptotic Protease-Activating Factor 1 / genetics*
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Autophagy / genetics*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspases / genetics*
  • Caspases / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation
  • History, 20th Century
  • History, 21st Century
  • Homeostasis / genetics
  • Humans
  • Microscopy, Electron / history
  • Microscopy, Electron / methods
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • BCL2 protein, human
  • Caenorhabditis elegans Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • ced-3 protein, C elegans