title: Mammalian Autophagy: How Does It Work?
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.
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Carla F
authors: CF
authors: Bento
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Maurizio
authors: M
authors: Renna
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Ghita
authors: G
authors: Ghislat
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Claudia
authors: C
authors: Puri
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Avraham
authors: A
authors: Ashkenazi
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Mariella
authors: M
authors: Vicinanza
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: Fiona M
authors: FM
authors: Menzies
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; email: dcr1000@cam.ac.uk.
authors: David C
authors: DC
authors: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism*; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008322:Mammals; D008958:Models, Molecular; D010588:Phagosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; D050600:SNARE Proteins; D058546:Class III Phosphatidylinositol 3-Kinases; D020691:rab GTP-Binding Proteins
keywords: autophagosome biogenesis; autophagy; endocytosis; lysosome; membrane trafficking; structural biology