title: Mitochondrial transporter responsiveness and metabolic flux homeostasis in postischemic hearts.
abstract: The transport of metabolites between mitochondria and cytosol via the alpha-ketoglutarate-malate carrier serves to balance flux between the two spans of the tricarboxylic acid (TCA) cycle but is reduced in stunned myocardium. To examine the mechanism for reduced transporter activity, we followed the postischemic response of metabolite influx/efflux from mitochondria to stimulation of the malate-aspartate (MA) shuttle. Isolated rabbit hearts were either perfused with 2.5 mM [2-13C]acetate (n = 7) or similarly reperfused (n = 5) after 10-min ischemia. In other hearts, the MA shuttle was stimulated with a high cytosolic redox state (NADH) induced by 2.5 mM lactate in normal (n = 6) or reperfused hearts (n = 7). In normal hearts, the MA shuttle response accelerated transport from 8.3 +/- 3.4 to 16.2 +/- 5.0 micromol. min(-1). g dry wt(-1). Although transport was reduced in stunned hearts, the MA shuttle was responsive to cytosolic NADH load, increasing transport from 3.4 +/- 1.0 to 9.8 +/- 3.7 micromol. min(-1). g dry wt(-1). Therefore, metabolite exchange remains intact in stunned myocardium but responds to changes in TCA cycle flux regulation.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: O'Donnell
authors.forename: L T
authors.initials: LT
authors.lastname: White
authors.forename: E D
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001692:Biological Transport; D008293:Malates / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D014233:Tricarboxylic Acids / Q000378:metabolism*
chemical_list: D008293:Malates; D014233:Tricarboxylic Acids; D001224:Aspartic Acid; C030298:malic acid