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.
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China.
Qinfang
Q
Shen
Fengsong
F
Qin
Zhiyang
Z
Gao
Jie
J
Cui
Hui
H
Xiao
Zhiheng
Z
Xu
Chonglin
C
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001278:Atractyloside / Q000494:pharmacology; D001865:Bongkrekic Acid / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017353:Gene Deletion; D015870:Gene Expression; D017238:Genes, Helminth; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D046912:Multiprotein Complexes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C087233:Ced-9 protein, C elegans; C112486:EGL-1 protein, C elegans; D046912:Multiprotein Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D001865:Bongkrekic Acid; D001278:Atractyloside; D000226:Mitochondrial ADP, ATP Translocases; D020169:Caspases; C089223:ced-3 protein, C elegans