This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Shen, Q.
Right arrow Articles by Yang, C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, Q.
Right arrow Articles by Yang, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2009, p. 3881-3893, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01509-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Adenine Nucleotide Translocator Cooperates with Core Cell Death Machinery To Promote Apoptosis in Caenorhabditis elegans{triangledown} ,{ddagger}

Qinfang Shen,1,2,{dagger} Fengsong Qin,1,2,{dagger} Zhiyang Gao,1,{dagger} Jie Cui,1,2 Hui Xiao,1,2 Zhiheng Xu,1 and Chonglin Yang1*

Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China,1 Graduate School, Chinese Academy of Sciences, Beijing 100039, China2

Received 27 September 2008/ Returned for modification 18 December 2008/ Accepted 28 April 2009

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.

* Corresponding author. Mailing address: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China. Phone: 86-10-64889375. Fax: 86-10-64856015. E-mail: clyang{at}genetics.ac.cn

{triangledown} Published ahead of print on 4 May 2009.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} Q.S., F.Q., and Z.G. contributed equally to this study.

Molecular and Cellular Biology, July 2009, p. 3881-3893, Vol. 29, No. 14
0270-7306/09/$08.00+0     doi:10.1128/MCB.01509-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»