Mitochondria as sensors of sphingolipids.
Much of the action in the mammalian apoptotic program takes place at the mitochondrial level. Physicochemical characteristics and integrity of mitochondrial membranes may play a crucial role in the recruitment and multimerization of pro-apoptotic Bcl-2 family members, opening of the permeability transition pore complex (PTPC) and the release of mitochondrial components which trigger the 'intrinsic' pathways of cellular apoptosis and activate executioner caspases. Recent evidence has accumulated pointing toward the mitochondrial membranes as the key targets for lipid and glycolipid mediators of stress-induced apoptosis. Mitochondrial membranes may thus act as 'sensors' of cellular stress by quantitating the local accumulation of specific lipids and glycolipids. Acute accumulation of ceramides, directly or indirectly, profoundly affects mitochondrial functions. GD3 ganglioside, a glycolipid which is actively synthesized and transiently accumulates in the early stages of apoptosis, relocates to the mitochondrial membranes causing the opening of the PTPC and the release of apoptogenic factors. Mitochondrial membranes appear to represent a common destination where protein and glycolipid mediators of stress converge and where crucial decisions about cellular adaptation or apoptotic cell death are taken.
Tomassini
Barbara
B
Laboratory of Immunology and Signal Transduction, Department of Experimental Medecine and Biochemical Science, University of Rome, Tor Vergata, Rome, Italy. tomassini@med.uniroma2.it
Testi
Roberto
R
D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D002518:Ceramides; D005732:Gangliosides; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013107:Sphingolipids; D019014:fas Receptor