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

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 (Vo(2)) was measured with respiratory calorimetry. Maximal oxygen uptake (Vo(2)max) was measured during maximal exercise on a cycle ergometer. Resting [ADP] was estimated from in vivo P-31 MRS measurements of inorganic phosphate, phosphocreatine, and ATP content of forearm muscle. Results: Resting Vo(2) was significantly increased in all three patients: 128 +/- 14% (SD) of values in healthy control subjects. Vo(2)max in patients was on average 2.8 times their Vo(2) at rest and was only 28% of Vo(2)max in control subjects. Resting [ADP] in forearm muscle was significantly increased compared with healthy control subjects (patients 26 +/- 2 muM, healthy controls 9 +/- 2 muM). 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).