title: Mitochondrial proton conductance in skeletal muscle of a cold-exposed marsupial, Antechinus flavipes, is unlikely to be involved in adaptive nonshivering thermogenesis but displays increased sensitivity toward carbon-centered radicals.
abstract: The organs and molecular mechanisms contributing to adaptive thermogenesis in marsupials are not known because some species apparently lack brown adipose tissue (BAT). The increased oxidative capacity and presence of uncoupling protein 3 (UCP3) in skeletal muscle led to speculations on whether uncoupled respiration sustains endothermy in the cold, as found for BAT. Here, we investigated the role of mitochondrial proton conductance in the small Australian marsupial Antechinus flavipes during cold exposure. Although there was a tendency toward higher oxidative capacity in skeletal muscle, indicating metabolic adjustments to the cold, we observed no change in basal proton conductance of isolated myotubular and liver mitochondria. In eutherians, 4-hydroxynonenal (HNE) is an activator of mitochondrial uncoupling mediated by UCP3 and ANT (adenine nucleotide translocase). In the marsupial A. flavipes, proton conductance in myotubular mitochondria could be induced by HNE selectively in the cold-acclimated group. Induced uncoupling activity could be attributed to the ANT as judged by inhibition with carboxyatractylate, while GDP, a putative inhibitor of rodent UCP3, had no detectable effects on marsupial UCP3. In contrast to previous expectations, basal proton conductance in the myotubular mitochondria of marsupials does not contribute to adaptive thermogenesis, as found for eutherian BAT. Increased sensitivity of proton conductance to HNE by the ANT suggests a greater requirement for mild uncoupling activity that may convey protection from lipid peroxidation and mitigate reactive oxygen species production during cold stress.
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Philipps-Universität Marburg, 35032 Marburg, Germany. mjastroch@buckinstitute.org
authors.forename: Martin
authors.initials: M
authors.lastname: Jastroch
authors.forename: Kerry W
authors.initials: KW
authors.lastname: Withers
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stoehr
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
mesh_terms: D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000502:physiology; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D003081:Cold Climate; D017931:DNA Primers / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D015227:Lipid Peroxidation; D008394:Marsupialia / Q000235:genetics / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D000071247:Uncoupling Protein 3
chemical_list: D000447:Aldehydes; D017931:DNA Primers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011522:Protons; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000071247:Uncoupling Protein 3; D001278:Atractyloside; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV; C027576:4-hydroxy-2-nonenal; C003853:carboxyatractyloside