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.
Shen
Qinfang
Q
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China.
Qin
Fengsong
F
Gao
Zhiyang
Z
Cui
Jie
J
Xiao
Hui
H
Xu
Zhiheng
Z
Yang
Chonglin
C
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