Tags

Type your tag names separated by a space and hit enter

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.
Am J Physiol Cell Physiol 2005; 288(5):C1074-82AJ

Abstract

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics.

Authors+Show Affiliations

Department of Physiology, Brody School of Medicine, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15647392

Citation

Koves, Timothy R., et al. "Subsarcolemmal and Intermyofibrillar Mitochondria Play Distinct Roles in Regulating Skeletal Muscle Fatty Acid Metabolism." American Journal of Physiology. Cell Physiology, vol. 288, no. 5, 2005, pp. C1074-82.
Koves TR, Noland RC, Bates AL, et al. Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. Am J Physiol, Cell Physiol. 2005;288(5):C1074-82.
Koves, T. R., Noland, R. C., Bates, A. L., Henes, S. T., Muoio, D. M., & Cortright, R. N. (2005). Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. American Journal of Physiology. Cell Physiology, 288(5), pp. C1074-82.
Koves TR, et al. Subsarcolemmal and Intermyofibrillar Mitochondria Play Distinct Roles in Regulating Skeletal Muscle Fatty Acid Metabolism. Am J Physiol, Cell Physiol. 2005;288(5):C1074-82. PubMed PMID: 15647392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism. AU - Koves,Timothy R, AU - Noland,Robert C, AU - Bates,Andrew L, AU - Henes,Sarah T, AU - Muoio,Deborah M, AU - Cortright,Ronald N, Y1 - 2005/01/12/ PY - 2005/1/14/pubmed PY - 2005/6/10/medline PY - 2005/1/14/entrez SP - C1074 EP - 82 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 288 IS - 5 N2 - Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics. SN - 0363-6143 UR - https://www.unboundmedicine.com/medline/citation/15647392/Subsarcolemmal_and_intermyofibrillar_mitochondria_play_distinct_roles_in_regulating_skeletal_muscle_fatty_acid_metabolism_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00391.2004?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -