Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans.

In Caenorhabditis elegans, the central cell-killing process is essentially controlled by the interplay of four apoptotic factors: EGL-1/BH3-only protein, CED-9/Bcl2, CED-4/Apaf1, and CED-3/caspase. In cells destined to die, EGL-1 binds to CED-9 and results in the release of CED-4 from the mitochondrion-tethered CED-9-CED-4 complex to the perinucleus, which facilitates processing ...
of the CED-3 caspase to cause apoptosis. However, whether additional factors exist to regulate the cell-killing process remains largely unknown. We have identified here WAN-1, the C. elegans ortholog of mammalian adenine nucleotide translocator, as an important cell death regulator. Genetic inactivation of wan-1 significantly suppressed both somatic and germ line cell deaths in C. elegans. Consistently, chemical inhibition of WAN-1 activity also caused strong reduction of germ line apoptosis. WAN-1 localizes to mitochondria and can form complex with both CED-4 and CED-9. Importantly, the cell death initiator EGL-1 can disrupt the interaction between CED-9 and WAN-1. In addition, overexpression of WAN-1 induced ectopic cell killing dependently on the core cell death pathway. These findings suggest that WAN-1 is involved in the central cell-killing process and cooperates with the core cell death machinery to promote programmed cell death in C. elegans.
Mesh Terms:
Animals, Apoptosis, Atractyloside, Bongkrekic Acid, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Caspases, Cell Line, Gene Deletion, Gene Expression, Genes, Helminth, Germ Cells, Humans, Mitochondria, Mitochondrial ADP, ATP Translocases, Multiprotein Complexes, Proto-Oncogene Proteins c-bcl-2, RNA Interference, Repressor Proteins
Mol Cell Biol
Date: Jul. 01, 2009
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