Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans.
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. Two major types of PCD have been distinguished: the caspase-mediated process of apoptosis and the caspase-independent process involving autophagy. Although apoptosis and autophagy are often activated together in response to stress, 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.
Takacs-Vellai
Krisztina
K
Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
Vellai
Tibor
T
Puoti
Alessandro
A
Passannante
Myriam
M
Wicky
Chantal
C
Streit
Adrian
A
Kovacs
Attila L
AL
Müller
Fritz
F
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing; D047468:Immunoprecipitation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D033921:Vesicular Transport Proteins; D051025:bcl-Associated Death Protein / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D033921:Vesicular Transport Proteins; D051025:bcl-Associated Death Protein; C477268:bec-1 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases