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

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.

Mitochondria Initiate and Regulate Sarcopenia

“…Cardiolipin is an important mitochondria-specific phospholipid, which is concentrated between inner and outer mitochondrial membranes, and redistribution of cardiolipin leads to a localized oligomerization of proapoptotic proteins (83). A local apoptotic cascade could occur via restricted remodeling and redistribution of cardiolipin adjacent to dysfunctional mitochondria.…”

Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome

“…The mechanisms that lead from abnormal CL biogenesis to cardiomyopathy are not well understood. They include dysregulation or dysfunction of numerous processes that are related to oxidative phosphorylation [ 20 , 30 , 31 ], fission or fusion [ 21 , 32 , 33 ], iron–sulfur cluster biogenesis [ 34 ], protein import [ 18 , 22 ], apoptosis [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ], autophagy [ 36 , 42 ], and transport of protein precursors across the mitochondrial membrane (in general metabolites) [ 18 , 23 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells

“…This disease is caused by mutations in Tafazzin, a mitochondrial protein involved in the remodeling of cardiolipin (CL). This phospholipid is mainly found in mitochondria, 4 5 6 7 8 9 10 where it optimizes numerous processes including oxidative phosphorylation (OXPHOS) 11 12 13 , fusion 14 , fission 15 16 , protein import 17 18 , iron-sulfur cluster biogenesis 19 , mitophagy 20 21 22 23 , apoptosis 7 23 24 25 26 27 28 and the transport of metabolites across the mitochondrial inner membrane 6 17 29 30 31 32 33 34 35 36 . Tafazzin is an acyltransferase required for the maintenance of unsaturated carbon-carbon bonds in CL fatty acyl chains 1 37 38 39 40 41 .…”