Inactivation of the mitochondrial carrier SLC25A25 (ATP-Mg2+/Pi transporter) reduces physical endurance and metabolic efficiency in mice

J Biol Chem. 2011 Apr 1;286(13):11659-71. doi: 10.1074/jbc.M110.203000. Epub 2011 Feb 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Adiposity / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cold-Shock Response / physiology
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Energy Metabolism / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Obesity / genetics
  • Obesity / metabolism
  • Physical Conditioning, Animal
  • Physical Endurance / physiology*
  • Thermogenesis / physiology*
  • Uncoupling Protein 1

Substances

  • Calcium-Binding Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Adenosine Triphosphate
  • Calcium