Maturation of autophagic vacuoles in Mammalian cells.
The autophagic process was first described in mammalian cells several decades ago. After their formation as double-membraned vacuoles containing cytoplasmic material, autophagic vacuoles or autophagosomes undergo a stepwise maturation including fusion with both endosomal and lysosomal vesicles. However, the molecular mechanisms regulating these fusion steps have begun to emerge only recently. The list of newly discovered molecules that regulate the maturation of autophagosomes to degradative autolysosomes includes the AAA ATPase SKD1, the small GTP binding protein Rab7, and possibly also the Alzheimer-linked presenilin 1. This review combines previous data on the endo/lysosomal fusion steps during autophagic vacuole maturation with recent findings on the molecules regulating these fusion steps. Interestingly, autophagic vacuole maturation appears to be blocked in certain human diseases including neuronal ceroid lipofuscinosis and Danon disease. This suggests that autophagy has important housekeeping or protective functions because a block in autophagic maturation causes a disease.
Eskelinen
Eeva-Liisa
EL
Institute of Biochemistry, University of Kiel, Germany. eleskelinen@biochem.uni-kiel.de
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000502:physiology* / Q000648:ultrastructure; D008561:Membrane Fusion; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000502:physiology* / Q000648:ultrastructure; D053764:Presenilin-1 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014617:Vacuoles / Q000502:physiology* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D056827:Endosomal Sorting Complexes Required for Transport; D051907:Lysosomal Membrane Proteins; D053764:Presenilin-1; D012097:Repressor Proteins; D033921:Vesicular Transport Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490304:VPS4B protein, human; C089217:Vps4b protein, mouse; D020691:rab GTP-Binding Proteins