Mammalian Autophagy: How Does It Work?

Annu Rev Biochem. 2016 Jun 2;85:685-713. doi: 10.1146/annurev-biochem-060815-014556. Epub 2016 Feb 8.

Abstract

Autophagy is a conserved intracellular pathway that delivers cytoplasmic contents to lysosomes for degradation via double-membrane autophagosomes. Autophagy substrates include organelles such as mitochondria, aggregate-prone proteins that cause neurodegeneration and various pathogens. Thus, this pathway appears to be relevant to the pathogenesis of diverse diseases, and its modulation may have therapeutic value. Here, we focus on the cell and molecular biology of mammalian autophagy and review the key proteins that regulate the process by discussing their roles and how these may be modulated by posttranslational modifications. We consider the membrane-trafficking events that impact autophagy and the questions relating to the sources of autophagosome membrane(s). Finally, we discuss data from structural studies and some of the insights these have provided.

Keywords: autophagosome biogenesis; autophagy; endocytosis; lysosome; membrane trafficking; structural biology.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Class III Phosphatidylinositol 3-Kinases / genetics
  • Class III Phosphatidylinositol 3-Kinases / metabolism*
  • Cytoskeleton / chemistry
  • Cytoskeleton / metabolism
  • Endocytosis
  • Humans
  • Lysosomes / metabolism
  • Mammals
  • Models, Molecular
  • Phagosomes / metabolism
  • Protein Processing, Post-Translational*
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Signal Transduction
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Autophagy-Related Proteins
  • SNARE Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • rab GTP-Binding Proteins