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Am J Physiol Regul Integr Comp Physiol 290: R1271-R1275, 2006. First published December 15, 2005; doi:10.1152/ajpregu.00651.2005
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis

Margus Eimre,1 Raivo Puhke,2 Karin Alev,2 Evelin Seppet,1 Anneli Sikkut,2 Nadezhda Peet,1 Lumme Kadaja,1 Aleks Lenzner,3 Tiit Haviko,3 Teet Seene,2 Valdur A. Saks,4,5 and Enn K. Seppet1

1Department of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, 2Department of Functional Morphology, Faculty of Exercise and Sport Science, 3Department of Traumatology and Orthopaedics, Faculty of Medicine, University of Tartu, Tartu, Estonia; 4Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia; and 5Laboratory of Bioenergetics, Joseph Fourier University, Grenoble, France

Submitted 6 September 2005 ; accepted in final form 9 December 2005

The cellular energy metabolism in human musculus gluteus medius (MGM) under normal conditions and hip osteoarthritis (OA) was explored. The functions of oxidative phosphorylation and energy transport systems were analyzed in permeabilized (skinned) muscle fibers by oxygraphy, in relation to myosin heavy chain (MHC) isoform distribution profile analyzed by SDS-PAGE, and to creatine kinase (CK) and adenylate kinase (AK) activities measured spectrophotometrically in the intact muscle. The results revealed high apparent Km for ADP in regulation of respiration that decreased after addition of creatine in MGM of traumatic patients (controls). OA was associated with increased sensitivity of mitochondrial respiration to ADP, decreased total activities of AK and CK with major reduction in mi-CK fraction, and attenuated effect of creatine on apparent Km for ADP compared with control group. It also included a complete loss of type II fibers in a subgroup of patients with the severest disease grade. It is concluded that energy metabolism in MGM cells is organized into functional complexes of mitochondria and ATPases. It is suggested that because of degenerative remodeling occurring during development of OA, these complexes become structurally and functionally impaired, which results in increased access of exogenous ADP to mitochondria and dysfunction of CK-phosphotransfer system.

musculus gluteus medius; myosin heavy chains; mitochondrial respiration; energy transfer


Address for reprint requests and other correspondence: E. K. Seppet, Dept. of Pathophysiology, Faculty of Medicine, Univ. of Tartu, 19 Ravila St., 50411 Tartu, Estonia (E-mail: enn.seppet{at}ut.ee)






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