Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1.
Beclin 1 has a key role in the initiation of autophagy, a process of self-cannibalism in which cytoplasmic constituents are sequestered and targeted for lysosomal degradation. In a recent issue of Cell Death & Disease, Wirawan et al. report the significant finding that caspases can cleave Beclin 1, thereby destroying its pro-autophagic activity. Moreover, the C-terminal fragment of Beclin 1 that results from this cleavage acquires a new function and can amplify mitochondrion-mediated apoptosis. Of note, the BH3 domain of Beclin 1 remains within the N-terminal fragment, which has no detectable pro-apoptotic activity. These findings provide important insights into the molecular cross talk between autophagy and apoptosis.
Djavaheri-Mergny
M
M
INSERM U916 VINCO, Institut Bergonié, Bordeaux 33076 France. mojgan.mergny@inserm.fr
Maiuri
M C
MC
Kroemer
G
G
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008247:Lysosomes / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D020169:Caspases