Altered Traffic of Cardiolipin during Apoptosis: Exposure on the Cell Surface as a Trigger for "Antiphospholipid Antibodies"

J Immunol Res. 2015:2015:847985. doi: 10.1155/2015/847985. Epub 2015 Sep 29.

Abstract

Apoptosis has been reported to induce changes in the remodelling of membrane lipids; after death receptor engagement, specific changes of lipid composition occur not only at the plasma membrane, but also in intracellular membranes. This paper focuses on one important aspect of apoptotic changes in cellular lipids, namely, the redistribution of the mitochondria-specific phospholipid, cardiolipin (CL). CL predominantly resides in the inner mitochondrial membrane, even if the rapid remodelling of its acyl chains and the subsequent degradation occur in other membrane organelles. After death receptor stimulation, CL appears to concentrate into mitochondrial "raft-like" microdomains at contact sites between inner and outer mitochondrial membranes, leading to local oligomerization of proapoptotic proteins, including Bid. Clustering of Bid in CL-enriched contacts sites is interconnected with pathways of CL remodelling that intersect membrane traffic routes dependent upon actin. In addition, CL association with cytoskeleton protein vimentin was observed. Such novel association also indicated that CL molecules may be expressed at the cell surface following apoptotic stimuli. This observation adds a novel implication of biomedical relevance. The association of CL with vimentin at the cell surface may represent a "new" target antigen in the context of the apoptotic origin of anti-vimentin/CL autoantibodies in Antiphospholipid Syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Antiphospholipid / immunology
  • Apoptosis / immunology*
  • Biological Transport
  • Cardiolipins / immunology*
  • Cardiolipins / metabolism*
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • Humans
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Phospholipids / immunology
  • Phospholipids / metabolism
  • Protein Binding
  • Signal Transduction
  • Vimentin / metabolism

Substances

  • Antibodies, Antiphospholipid
  • Cardiolipins
  • Phospholipids
  • Vimentin