Inhibition of Macroautophagy Triggers Apoptosis

Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or monensin). Cell death occurred through apoptosis (type 1 cell death), since it was reduced by stabilization of mitochondrial membranes (with Bcl-2 or vMIA, a cytomegalovirus-derived gene) or by caspase inhibition. Under conditions in which the fusion between lysosomes and autophagosomes was inhibited, the formation of autophagic vacuoles was enhanced at a preapoptotic stage, as indicated by…

• YU
  Yale University
• I
  ImmunoGen
• EC
  European Commission

  Award: QLK3-CT-2002-01956
• IG
  Institut Gustave-Roussy
• NI
  National Institutes of Health
• NI
  National Institute of Child Health and Human Development