Overview of macroautophagy regulation in mammalian cells

Cell Res. 2010 Jul;20(7):748-62. doi: 10.1038/cr.2010.82. Epub 2010 Jun 15.


Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of autophagy is now better understood because of the discovery that the activity of Atg complexes is targeted by protein kinases, and owing to the importance of nuclear regulation via transcription factors in regulating the expression of autophagy genes.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / genetics
  • Autophagy / physiology*
  • Beclin-1
  • E2F1 Transcription Factor / physiology
  • Endocytosis / physiology
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Forkhead Transcription Factors / physiology
  • Humans
  • Hypoxia-Inducible Factor 1 / physiology
  • Inositol 1,4,5-Trisphosphate Receptors / physiology
  • Intracellular Signaling Peptides and Proteins / physiology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lysosomes / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • N-Ethylmaleimide-Sensitive Proteins / metabolism
  • NF-kappa B / metabolism
  • Phagosomes / genetics
  • Phagosomes / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins / physiology
  • Vacuolar Sorting Protein VPS15


  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • E2F1 Transcription Factor
  • Endosomal Sorting Complexes Required for Transport
  • Forkhead Transcription Factors
  • Hypoxia-Inducible Factor 1
  • Inositol 1,4,5-Trisphosphate Receptors
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • UVRAG protein, mouse
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • PIK3R4 protein, human
  • Pik3r4 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Vacuolar Sorting Protein VPS15
  • JNK Mitogen-Activated Protein Kinases
  • N-Ethylmaleimide-Sensitive Proteins