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Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans.
Mol Cell Biol. 2009 Jul; 29(14):3881-93.MC

Abstract

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.

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Authors+Show Affiliations

Shen Q
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China.
Qin F
No affiliation info available
Gao Z
No affiliation info available
Cui J
No affiliation info available
Xiao H
No affiliation info available
Xu Z
No affiliation info available
Yang C
No affiliation info available

MeSH

AnimalsApoptosisAtractylosideBongkrekic AcidCaenorhabditis elegansCaenorhabditis elegans ProteinsCalcium-Binding ProteinsCaspasesCell LineGene DeletionGene ExpressionGenes, HelminthGerm CellsHumansMitochondriaMitochondrial ADP, ATP TranslocasesMultiprotein ComplexesProto-Oncogene Proteins c-bcl-2RNA InterferenceRepressor Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19414600

Citation

Shen, Qinfang, et al. "Adenine Nucleotide Translocator Cooperates With Core Cell Death Machinery to Promote Apoptosis in Caenorhabditis Elegans." Molecular and Cellular Biology, vol. 29, no. 14, 2009, pp. 3881-93.
Shen Q, Qin F, Gao Z, et al. Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans. Mol Cell Biol. 2009;29(14):3881-93.
Shen, Q., Qin, F., Gao, Z., Cui, J., Xiao, H., Xu, Z., & Yang, C. (2009). Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans. Molecular and Cellular Biology, 29(14), 3881-93. https://doi.org/10.1128/MCB.01509-08
Shen Q, et al. Adenine Nucleotide Translocator Cooperates With Core Cell Death Machinery to Promote Apoptosis in Caenorhabditis Elegans. Mol Cell Biol. 2009;29(14):3881-93. PubMed PMID: 19414600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans. AU - Shen,Qinfang, AU - Qin,Fengsong, AU - Gao,Zhiyang, AU - Cui,Jie, AU - Xiao,Hui, AU - Xu,Zhiheng, AU - Yang,Chonglin, Y1 - 2009/05/04/ PY - 2009/5/6/entrez PY - 2009/5/6/pubmed PY - 2009/7/14/medline SP - 3881 EP - 93 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 29 IS - 14 N2 - 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. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/19414600/Adenine_nucleotide_translocator_cooperates_with_core_cell_death_machinery_to_promote_apoptosis_in_Caenorhabditis_elegans_ L2 - https://journals.asm.org/doi/10.1128/MCB.01509-08?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -