Altered Traffic of Cardiolipin during Apoptosis: Exposure on the Cell Surface as a Trigger for "Antiphospholipid Antibodies".
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.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Valeria
V
Manganelli
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Antonella
A
Capozzi
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Serena
S
Recalchi
Department of Hematology, Oncology and Molecular Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Michele
M
Signore
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy ; Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, Via dell'Elettronica, 02100 Rieti, Italy.
Vincenzo
V
Mattei
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Tina
T
Garofalo
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Roberta
R
Misasi
Italian Institute of Technology, Via Morego 30, 16136 Genoa, Italy.
Mauro
M
Degli Esposti
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Maurizio
M
Sorice
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001692:Biological Transport; D002308:Cardiolipins / Q000276:immunology* / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D014746:Vimentin / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D010743:Phospholipids; D014746:Vimentin