Muscular mitochondrial function in amyotrophic lateral sclerosis is progressively altered as the disease develops: a temporal study in man.
We performed repeated analysis of mitochondrial respiratory function in skeletal muscle (SM) of patients with early-stage sporadic amyotrophic lateral sclerosis (SALS) to determine whether mitochondrial function was altered as the disease advanced. SM biopsies were obtained from 7 patients with newly diagnosed SALS, the same 7 patients 3 months later, and 7 sedentary controls. Muscle fibers were permeabilized with saponin, then skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated respiration rates and to assess mitochondrial regulation by ADP. We found that the maximal oxidative phosphorylation capacity of muscular mitochondria significantly increased, and muscular mitochondrial respiratory complex IV activity significantly decreased as the disease advanced. This temporal study demonstrates for the first time that mitochondrial function in SM in human SALS is progressively altered as the disease develops.
Echaniz-Laguna
Andoni
A
Département de Neurologie, Hôpital Civil de Strasbourg, 1 Place de l'Hôpital, BP426, 67091 Strasbourg, France. Echaniz-Laguna@medecine.u-strasbg.fr
Zoll
Joffrey
J
Ponsot
Elodie
E
N'guessan
Benoit
B
Tranchant
Christine
C
Loeffler
Jean-Philippe
JP
Lampert
Eliane
E
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D016022:Case-Control Studies; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D004576:Electromyography / Q000379:methods; D005080:Exercise Test / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000473:pathology*; D009097:Multienzyme Complexes / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*
D009097:Multienzyme Complexes