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Impaired control of respiration in iron-deficient muscle mitochondria
1Department of Pediatrics, School of Medicine, University of California, San Francisco 94143.
Abstract:
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.
Insights
Dietary iron deficiency impairs skeletal muscle mitochondrial respiration and alters exercise-induced muscle fiber recruitment. Iron repletion partially restores respiratory control, suggesting its importance in exercise adaptation.
Area of Science:
- Exercise Physiology
- Mitochondrial Biology
- Nutritional Biochemistry
Background:
- Dietary iron deficiency (ID) reduces iron-containing proteins, impacting skeletal muscle mitochondrial respiration.
- Non-iron components of skeletal muscle mitochondria are less affected by iron deficiency.
Purpose of the Study:
- To investigate the effects of iron deficiency on skeletal muscle mitochondrial respiration control.
- To examine the consequences of impaired respiratory control on motor unit recruitment during exercise.
Main Methods:
- Isolated skeletal muscle mitochondria (SMM) from rats with varying iron status were studied using an ATP-utilizing system.
- Respiratory control sensitivity was assessed via titration with carboxyatractyloside, an adenine nucleotide translocase (AdNT) inhibitor.
- Rats underwent treadmill exercise to evaluate exercise-induced adaptations in muscle fibers.
Main Results:
- Iron deficiency reduced the turnover number of AdNT, impairing mitochondrial respiratory control sensitivity.
- Iron repletion improved AdNT turnover and respiratory control.
- Exercise induced significant mitochondrial enzyme adaptations in iron-deficient rats, particularly in fast glycolytic muscle fibers, suggesting altered motor unit recruitment patterns.
Conclusions:
- Impaired skeletal muscle mitochondrial respiratory capacity in iron deficiency is linked to reduced AdNT turnover and sensitivity.
- Altered motor unit recruitment during exercise in iron deficiency may be influenced by impaired mitochondrial respiratory control sensitivity.
- Skeletal muscle mitochondrial respiratory control sensitivity is a key factor in motor unit recruitment during aerobic exercise.