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 (31)P 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 microM, healthy controls 9 +/- 2 microM). 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).
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 (31)P 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 microM, healthy controls 9 +/- 2 microM). 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).
Authors: Cecile Vernochet; Arnaud Mourier; Olivier Bezy; Yazmin Macotela; Jeremie Boucher; Matthew J Rardin; Ding An; Kevin Y Lee; Olga R Ilkayeva; Cristina M Zingaretti; Brice Emanuelli; Graham Smyth; Saverio Cinti; Christopher B Newgard; Bradford W Gibson; Nils-Göran Larsson; C Ronald Kahn Journal: Cell Metab Date: 2012-11-15 Impact factor: 27.287
Authors: Joep P J Schmitz; Natal A W van Riel; Klaas Nicolay; Peter A J Hilbers; Jeroen A L Jeneson Journal: Exp Physiol Date: 2009-10-02 Impact factor: 2.969