title: Inactivation of the mitochondrial carrier SLC25A25 (ATP-Mg2+/Pi transporter) reduces physical endurance and metabolic efficiency in mice.
abstract: An ATP-Mg(2+/)P(i) inner mitochondrial membrane solute transporter (SLC25A25), which is induced during adaptation to cold stress in the skeletal muscle of mice with defective UCP1/brown adipose tissue thermogenesis, has been evaluated for its role in metabolic efficiency. SLC25A25 is thought to control ATP homeostasis by functioning as a Ca(2+)-regulated shuttle of ATP-Mg(2+) and P(i) across the inner mitochondrial membrane. Mice with an inactivated Slc25a25 gene have reduced metabolic efficiency as evidenced by enhanced resistance to diet-induced obesity and impaired exercise performance on a treadmill. Mouse embryo fibroblasts from Slc25a25(-/-) mice have reduced Ca(2+) flux across the endoplasmic reticulum, basal mitochondrial respiration, and ATP content. Although Slc25a25(-/-) mice are metabolically inefficient, the source of the inefficiency is not from a primary function in thermogenesis, because Slc25a25(-/-) mice maintain body temperature upon acute exposure to the cold (4 °C). Rather, the role of SLC25A25 in metabolic efficiency is most likely linked to muscle function as evidenced from the physical endurance test of mutant mice on a treadmill. Consequently, in the absence of SLC25A25 the efficiency of ATP production required for skeletal muscle function is diminished with secondary effects on adiposity. However, in the absence of UCP1-based thermogenesis, induction of Slc25a25 in mice with an intact gene may contribute to an alternative thermogenic pathway for the maintenance of body temperature during cold stress.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
authors.forename: Rea P
authors.initials: RP
authors.lastname: Anunciado-Koza
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhang
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
authors.forename: Sudip
authors.initials: S
authors.lastname: Bajpeyi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koza
authors.forename: Richard C
authors.initials: RC
authors.lastname: Rogers
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D058639:Cold-Shock Response / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D010807:Physical Endurance / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology*; D000071256:Uncoupling Protein 1
chemical_list: D002135:Calcium-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000255:Adenosine Triphosphate; D002118:Calcium