Uncoupling protein-1 (UCP1) contributes to the basal proton conductance of brown adipose tissue mitochondria

Nadeene Parker, Paul G. Crichton, Antonio J. Vidal-Puig, Martin D. Brand

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Abstract

Proton leak pathways uncouple substrate oxidation from ATP synthesis in mitochondria. These pathways are classified as basal (not regulated) or inducible (activated and inhibited). Previously it was found that over half of the basal proton conductance of muscle mitochondria was catalyzed by the adenine nucleotide translocase (ANT), an abundant mitochondrial anion carrier protein. To determine whether ANT is the unique protein catalyst, or one of many proteins that catalyze basal proton conductance, we measured proton leak kinetics in mitochondria isolated from brown adipose tissue (BAT). BAT can express another mitochondrial anion carrier, UCP1, at concentrations similar to ANT. Basal proton conductance was measured under conditions where UCP1 and ANT were catalytically inactive and was found to be lower in mitochondria from UCP1 knockout mice compared to wild-type. Ablation of another abundant inner membrane protein, nicotinamide nucleotide transhydrogenase, had no effect on proton leak kinetics in mitochondria from liver, kidney or muscle, showing that basal proton conductance is not catalyzed by all membrane proteins. We identify UCP1 as a second protein propagating basal proton leak, lending support to the hypothesis that basal leak pathways are perpetrated by members of the mitochondrial anion carrier family but not by other mitochondrial inner membrane proteins.

Original languageEnglish
Article number335
JournalJournal of Bioenergetics and Biomembranes
Volume41
Early online date25 Aug 2009
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Adenine nucleotide translocase (ANT)
  • Brown adipose tissue (BAT)
  • Carboxyatractylate (CAT)
  • Nicotinamide nucleotide transhydrogenase (NNT)
  • Proton leak
  • Uncoupling protein (UCP)

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