C. elegans to model autophagy-related human disorders

Prog Mol Biol Transl Sci. 2020:172:325-373. doi: 10.1016/bs.pmbts.2020.01.007. Epub 2020 Apr 6.

Abstract

Autophagy is a highly conserved degradation process that clears damaged intracellular macromolecules and organelles in order to maintain cellular health. Dysfunctional autophagy is fundamentally linked to the development of various human disorders and pathologies. The use of the nematode Caenorhabditis elegans as a model system to study autophagy has improved our understanding of its regulation and function in organismal physiology. Here, we review the genetic, functional, and regulatory conservation of the autophagy pathway in C. elegans and we describe tools to quantify and study the autophagy process in this incredibly useful model organism. We further discuss how these nematodes have been modified to model autophagy-related human diseases and underscore the important insights obtained from such models. Altogether, we highlight the strengths of C. elegans as an exceptional tool to understand the genetic and molecular foundations underlying autophagy-related human diseases.

Keywords: Aging; Autophagy; Autophagy detection tools; Autophagy-related pathologies; C. elegans; Conserved mechanisms; Lifespan; Lysosome; Nematode.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Aging / genetics
  • Aging / physiology
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Autophagosomes / physiology
  • Autophagy* / genetics
  • Autophagy* / physiology
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / physiology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology
  • Gene Expression Regulation, Developmental
  • Genetic Engineering / methods
  • Humans
  • Immunity, Innate
  • Infections / genetics
  • Infections / pathology
  • Inflammation / genetics
  • Inflammation / pathology
  • Larva
  • Lysosomes / physiology
  • Models, Animal*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Peptides / physiology
  • Recombinant Proteins / metabolism
  • Species Specificity

Substances

  • Autophagy-Related Proteins
  • Caenorhabditis elegans Proteins
  • Peptides
  • Recombinant Proteins
  • polyglutamine