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Resting oxygen consumption and in vivo ADP are increased in myopathy due to complex I deficiency

From the Department of Pediatric Gastroenterology (Dr. Roef) and Laboratory for Metabolic Diseases (Dr. Berger), University Children’s Hospital, Utrecht; Laboratory for Metabolic Diseases (Dr. Reijngoud), Department of Pediatrics, University Hospital Groningen; and Department of Clinical Chemistry (Dr. de Meer), Vrije Universiteit Medical Center, Amsterdam, the Netherlands; and Department of Bioengineering (Dr. Jeneson), School of Medicine, University of Washington, Seattle.

Address correspondence and reprint requests to Dr. K. de Meer, Department of Clinical Chemistry, Reception K, Vrije Universiteit Medical Center, P.O. Box 7057, 1107 MB, Amsterdam, the Netherlands; e-mail: k.demeer{at}vumc.nl

Background: Patients with isolated complex I deficiency (CID) in skeletal muscle mitochondria often present with exercise intolerance as their major clinical symptom.

Objective: To study the in vivo bioenergetics in patients with complex I deficiency in skeletal muscle mitochondria.

Methods: In vivo bioenergetics were studied in three of these patients by measuring oxygen uptake at rest and during maximal exercise, together with forearm ADP concentrations ([ADP]) at rest. Whole-body oxygen consumption at rest (VO₂) was measured with respiratory calorimetry. Maximal oxygen uptake (VO₂max) was measured during maximal exercise on a cycle ergometer. Resting [ADP] was estimated from in vivo ³¹P MRS measurements of inorganic phosphate, phosphocreatine, and ATP content of forearm muscle.

Results: Resting VO₂ was significantly increased in all three patients: 128 ± 14% (SD) of values in healthy control subjects. VO₂max in patients was on average 2.8 times their VO₂ at rest and was only 28% of VO₂max in control subjects. Resting [ADP] in forearm muscle was significantly increased compared with healthy control subjects (patients 26 ± 2 µM, healthy controls 9 ± 2 µM).

Conclusion: In patients with CID, the increased whole-body oxygen consumption rate at rest reflects increased electron transport through the respiratory chain, driven by a decreased phosphorylation potential. The increased electron transport rate may compensate for the decreased efficiency of oxidative phosphorylation (phosphorylation potential).

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				F. Wu, J. A. L. Jeneson, and D. A. Beard Oxidative ATP synthesis in skeletal muscle is controlled by substrate feedback Am J Physiol Cell Physiol, January 1, 2007; 292(1): C115 - C124. [Abstract] [Full Text] [PDF]