Lipotoxicity, fatty acid uncoupling and mitochondrial carrier function.
Diseases like obesity, diabetes or generalized lipodystrophy cause a chronic elevation of circulating fatty acids that can become cytotoxic, a condition known as lipotoxicity. Fatty acids cause oxidative stress and alterations in mitochondrial structure and function. The uncoupling of the oxidative phosphorylation is one of the most recognized deleterious fatty acid effects and several metabolite transporters are known to mediate in their action. The fatty acid interaction with the carriers leads to membrane depolarization and/or the conversion of the carrier into a pore. The result is the opening of the permeability transition pore and the initiation of apoptosis. Unlike the other members of the mitochondrial carrier superfamily, the eutherian uncoupling protein UCP1 has evolved to achieve its heat-generating capacity in the physiological context provided by the brown adipocyte and therefore it is activated by the low fatty acid concentrations generated by the noradrenaline-stimulated lipolysis.
Rial
Eduardo
E
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain. rial@cib.csic.es
Rodríguez-Sánchez
Leonor
L
Gallardo-Vara
Eunate
E
Zaragoza
Pilar
P
Moyano
Eva
E
González-Barroso
M Mar
MM
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects; D010802:Phylogeny; D014475:Uncoupling Agents / Q000378:metabolism / Q000633:toxicity; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1