Adenine Nucleotide Translocator Cooperates with Core Cell death Machinery to Promote Apoptosis in C. elegans
Qinfang Shen,Fengsong Qin,Zhiyang Gao,Jie Cui,Hui Xiao,Zhiheng Xu,and Chonglin Yang
Mol. Cell. Biol
In C. 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 mitochondria-tethered CED-9-CED-4 complex to 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. Here we have identified WAN-1, the C. elegans ortholog of mammalian adenine nucleotide translocator (ANT), as an important cell death regulator. Genetic inactivation of wan-1 significantly suppressed both somatic and germline cell deaths in C. elegans. Consistently, chemical inhibition of WAN-1 activity also caused strong reduction of germline 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.