[PDF][PDF] Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans

K Takacs-Vellai, T Vellai, A Puoti, M Passannante… - Current biology, 2005 - cell.com
K Takacs-Vellai, T Vellai, A Puoti, M Passannante, C Wicky, A Streit, AL Kovacs, F Müller
Current biology, 2005cell.com
Programmed cell death (PCD) is an essential and highly orchestrated process that plays a
major role in morphogenesis and tissue homeostasis during development. In humans,
defects in regulation or execution of cell death lead to diabetes, neurodegenerative
disorders, and cancer [1]. Two major types of PCD have been distinguished: the caspase-
mediated process of apoptosis and the caspase-independent process involving autophagy
[1, 2]. Although apoptosis and autophagy are often activated together in response to stress …
Summary
Programmed cell death (PCD) is an essential and highly orchestrated process that plays a major role in morphogenesis and tissue homeostasis during development. In humans, defects in regulation or execution of cell death lead to diabetes, neurodegenerative disorders, and cancer [1]. Two major types of PCD have been distinguished: the caspase-mediated process of apoptosis and the caspase-independent process involving autophagy [1, 2]. Although apoptosis and autophagy are often activated together in response to stress [3], the molecular mechanisms underlying their interplay remain unclear. Here we show that BEC-1, the C. elegans ortholog of the yeast and mammalian autophagy proteins Atg6/Vps30 and Beclin 1, is essential for development. We demonstrate that BEC-1 is necessary for the function of the class III PI3 kinase LET-512/Vps34, an essential protein required for autophagy, membrane trafficking, and endocytosis. Furthermore, BEC-1 forms a complex with the antiapoptotic protein CED-9/Bcl-2, and its depletion triggers CED-3/Caspase-dependent PCD. Based on our results, we propose that bec-1 represents a link between autophagy and apoptosis, thus supporting the view that the two processes act in concerted manner in the cell death machinery.
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