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

Nat Cell Biol. 2007 May;9(5):541-9. doi: 10.1038/ncb1574. Epub 2007 Apr 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Apoptosis*
  • Biological Transport
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Membrane / metabolism
  • Germ Cells / enzymology
  • Germ Cells / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Mutation
  • Phosphatidylserines / metabolism*
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*
  • RNA Interference
  • Staining and Labeling / methods
  • Time Factors

Substances

  • Annexin A5
  • CED-2 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Phosphatidylserines
  • Phospholipid Transfer Proteins
  • SCRM-1 protein, C elegans
  • Wah-1 protein, C elegans
  • ced-1 protein, C elegans
  • Caspases
  • ced-3 protein, C elegans