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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78 Scopus citations

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 1 2007

ASJC Scopus subject areas

  • Cell Biology

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    Wang, X., Wang, J., Gengyo-Ando, K., Gu, L., Sun, C. L., Yang, C., Shi, Y., Kobayashi, T., Shi, Y., Mitani, S., Xie, X. S., & Xue, D. (2007). C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. Nature cell biology, 9(5), 541-549. https://doi.org/10.1038/ncb1574