Undecanesulfonate does not allosterically activate H+ uniport mediated by uncoupling protein-1 in brown adipose tissue mitochondria.
Undecanesulfonate is transported by uncoupling protein-1. Its inability to induce H+ uniport with reconstituted uncoupling protein-1 supports fatty acid cycling hypothesis. Rial et al. [Rial, E., Aguirregoitia, E., Jimenez-Jimenez, J., & Ledesma, A. (2004). Alkylsulfonates activate the uncoupling protein UCP1: Implications for the transport mechanism. Biochimica et Biophysica Acta, 1608, 122-130], have challenged the fatty acid cycling by observing uncoupling of brown adipose tissue mitochondria due to undecanesulfonate, interpreted as allosteric activation of uncoupling protein-1. We have estimated undecanesulfonate effects after elimination of endogenous fatty acids by carnitine cycle in the presence or absence of bovine serum albumin. We show that the undecanesulfonate effect is partly due to fatty acid release from albumin when undecanesulfonate releases bound fatty acid and partly represents a non-specific uncoupling protein-independent acceleration of respiration, since it proceeds also in rat heart mitochondria lacking uncoupling protein-1 and membrane potential is not decreased upon addition of undecanesulfonate without albumin. When the net fatty acid-induced uncoupling was assayed, the addition of undecanesulfonate even slightly inhibited the uncoupled respiration. We conclude that undecanesulfonate does not allosterically activate uncoupling protein-1 and that fatty acid cycling cannot be excluded on a basis of its non-specific effects.
Jezek
Petr
P
Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220 Prague 4, Czech Republic. jezek@biomed.cas.cz
Spacek
Tomás
T
Garlid
Keith
K
Jabůrek
Martin
M
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000476:Alkanesulfonates / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D005227:Fatty Acids / Q000378:metabolism; D007473:Ion Channels; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D024101:Mitochondrial Proteins; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D011522:Protons; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D000476:Alkanesulfonates; D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011522:Protons; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D012710:Serum Albumin, Bovine