Difference between revisions of "Miotto 2016 Biochem J"
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|title=Miotto PM, Holloway GP (2016) In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport. Biochem J 473:2831-43. | |title=Miotto PM, Holloway GP (2016) In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport. Biochem J 473:2831-43. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/27402793 PMID: 27402793] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/27402793 PMID: 27402793] | ||
|authors=Miotto PM, Holloway GP | |authors=Miotto PM, Holloway GP | ||
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© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. | © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. | ||
|keywords=ADP sensitivity, Adenine nucleotide translocase, Exercise metabolism, Mitochondrial bioenergetics, Mitochondrial respiration, Skeletal muscle | |keywords=ADP sensitivity, Adenine nucleotide translocase, Exercise metabolism, Mitochondrial bioenergetics, Mitochondrial respiration, Skeletal muscle, Blebbistatin | ||
|mipnetlab=CA Guelph Holloway GP | |mipnetlab=CA Guelph Holloway GP | ||
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|substratestates=CI, CI&II | |substratestates=CI, CI&II | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2016-09 | ||
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Revision as of 14:42, 20 September 2016
| Miotto PM, Holloway GP (2016) In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport. Biochem J 473:2831-43. |
Miotto PM, Holloway GP (2016) Biochem J
Abstract: The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr-independent ADP transport during exercise remains unknown. Therefore, we utilized an Mi-CK knockout (KO) model to determine whether in vivo Cr-independent mechanisms are biologically important for sustaining energy homeostasis during exercise. Ablating Mi-CK did not alter exercise tolerance, as the time to volitional fatigue was similar between wild-type (WT) and KO mice at various exercise intensities. In addition, skeletal muscle metabolic profiles after exercise, including glycogen, PCr/Cr ratios, free ADP/adenosine monophosphate (AMP), and lactate, were similar between genotypes. While these data suggest that the absence of PCr/Cr shuttling is not detrimental to maintaining energy homeostasis during exercise, KO mice displayed a dramatic increase in Cr-independent mitochondrial ADP sensitivity after exercise. Specifically, whereas mitochondrial ADP sensitivity decreased with exercise in WT mice, in stark contrast, exercise increased mitochondrial Cr-independent ADP sensitivity in KO mice. As a result, the apparent ADP Km was 50% lower in KO mice after exercise, suggesting that in vivo activation of voltage-dependent anion channel (VDAC)/adenine nucleotide translocase (ANT) can support mitochondrial ADP transport. Altogether, we provide insight that Cr-independent ADP transport mechanisms are biologically important for regulating ADP sensitivity during exercise, while highlighting complex regulation and the plasticity of the VDAC/ANT axis to support adenosine triphosphate demand.
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. • Keywords: ADP sensitivity, Adenine nucleotide translocase, Exercise metabolism, Mitochondrial bioenergetics, Mitochondrial respiration, Skeletal muscle, Blebbistatin
• O2k-Network Lab: CA Guelph Holloway GP
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase
Regulation: ADP, AMP, Inhibitor, PCr;Cr
Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k
2016-09
