title: Uncoupling protein-1 (UCP1) contributes to the basal proton conductance of brown adipose tissue mitochondria.
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.
authors.affiliation: MRC Mitochondrial Biology Unit, Wellcome Trust / MRC Building, Hills Road, Cambridge, CB2 0XY, UK. n.parker@ucl.ac.uk
authors.forename: Nadeene
authors.initials: N
authors.lastname: Parker
authors.forename: Paul G
authors.initials: PG
authors.lastname: Crichton
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Vidal-Puig
authors.forename: Martin D
authors.initials: MD
authors.lastname: Brand
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011522:Protons; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D011522:Protons; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
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