Impaired control of respiration in iron-deficient muscle mitochondria.
Dietary iron deficiency (ID) decreases iron-containing proteins and hence respiratory capacity of skeletal muscle mitochondria (SMM), but noniron components are much less affected. Using a hexokinase plus glucose ATP-utilizing system, we studied control of respiration in isolated SMM from rats of variable iron status: ID, ID 3 days after intraperitoneal treatment with iron dextran, and control. We found that sensitivity of respiratory control (e.g., ATP/ADP at a given oxygen consumption) was positively related to state 3 respiratory capacity. Titration studies with carboxyatractyloside, a noncompetitive inhibitor of adenine nucleotide translocase (AdNT), revealed that AdNT concentration was unaffected by iron status. However, the turnover number of AdNT was markedly reduced by ID and improved with iron treatment. We conclude that in ID SMM, decreased maximal respiratory capacity is paralleled by impaired sensitivity to putative controllers of oxidative phosphorylation at any respiratory rate, despite normal levels of AdNT. A second study was designed to determine possible consequences of impaired sensitivity of respiratory control on motor unit recruitment during exercise. ID and normal rats were subjected to a program of walking treadmill exercise. Although exercise failed to induce any changes in oxidative enzyme levels in control rat, ID animals and exhibited substantial mitochondrial enzyme adaptation in hindlimb skeletal muscle. Furthermore, the most consistent enzymatic changes were observed to occur in fast glycolytic muscle fibers. These results suggest marked alterations in the pattern of muscle fiber recruitment during mild exercise in ID rodents and support the hypothesis that sensitivity of respiratory control in SMM is an important determinant of motor unit recruitment during aerobic exercise.
Willis
W T
WT
Department of Pediatrics, School of Medicine, University of California, San Francisco 94143.
Dallman
P R
PR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D007501:Iron / Q000494:pharmacology; D000090463:Iron Deficiencies; D007700:Kinetics; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D007501:Iron