C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1

Xiaochen Wang, Jin Wang, Keiko Gengyo-Ando, Lichuan Gu, Chun Ling Sun, Chonglin Yang, Yong Shi, Tetsuo Kobayashi, Yigong Shi, Shohei Mitani, Xiao Song Xie, Ding Xue

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Abstract

Externalization of phosphatidylserine, which is normally restricted to the inner leaflet of plasma membrane, is a hallmark of mammalian apoptosis. It is not known what activates and mediates the phosphatidylserine externalization process in apoptotic cells. Here, we report the development of an annexin V-based phosphatidylserine labelling method and show that a majority of apoptotic germ cells in Caenorhabditis elegans have surface-exposed phosphatidylserine, indicating that phosphatidylserine externalization is a conserved apoptotic event in worms. Importantly, inactivation of the gene encoding either the C. elegans apoptosis-inducing factor (AIF) homologue (WAH-1), a mitochondrial apoptogenic factor, or the C. elegans phospholipid scramblase 1 (SCRM-1), a plasma membrane protein, reduces phosphatidylserine exposure on the surface of apoptotic germ cells and compromises cell-corpse engulfment. WAH-1 associates with SCRM-1 and activates its phospholipid scrambling activity in vitro. Thus WAH-1, after its release from mitochondria during apoptosis, promotes plasma membrane phosphatidylserine externalization through its downstream effector, SCRM-1.

Original languageEnglish (US)
Pages (from-to)541-549
Number of pages9
JournalNature Cell Biology
Volume9
Issue number5
DOIs
StatePublished - May 2007

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Phospholipid Transfer Proteins
Phosphatidylserines
Caenorhabditis elegans
Cell Membrane
Germ Cells
Apoptosis Inducing Factor
Apoptosis
Annexin A5
Gene Silencing
Cadaver
Blood Proteins
Phospholipids
Mitochondria
Membrane Proteins

ASJC Scopus subject areas

  • Cell Biology

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C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. / Wang, Xiaochen; Wang, Jin; Gengyo-Ando, Keiko; Gu, Lichuan; Sun, Chun Ling; Yang, Chonglin; Shi, Yong; Kobayashi, Tetsuo; Shi, Yigong; Mitani, Shohei; Xie, Xiao Song; Xue, Ding.

In: Nature Cell Biology, Vol. 9, No. 5, 05.2007, p. 541-549.

Research output: Contribution to journalArticle

Wang, X, Wang, J, Gengyo-Ando, K, Gu, L, Sun, CL, Yang, C, Shi, Y, Kobayashi, T, Shi, Y, Mitani, S, Xie, XS & Xue, D 2007, 'C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1', Nature Cell Biology, vol. 9, no. 5, pp. 541-549. https://doi.org/10.1038/ncb1574
Wang, Xiaochen ; Wang, Jin ; Gengyo-Ando, Keiko ; Gu, Lichuan ; Sun, Chun Ling ; Yang, Chonglin ; Shi, Yong ; Kobayashi, Tetsuo ; Shi, Yigong ; Mitani, Shohei ; Xie, Xiao Song ; Xue, Ding. / C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. In: Nature Cell Biology. 2007 ; Vol. 9, No. 5. pp. 541-549.
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