(A) Relative mRNA expression levels were determined by quantitative real-time PCR for VEGF, catalase, and SOD2 in gastrocnemius isolated from SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals throughout disease. Data are presented as mean ± SEM. See also Figure S1.
(B) Relative numbers of acetylcholine receptor (AChR) clusters per section of gastrocnemius were determined by staining with α-bungarotoxin. Data are presented as mean ± SEM.
(C) Electron micrographs from cross-sections taken from tibialis anterior muscle of SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at asymptomatic (4 months) and end-stage of disease (13–14 months). Scale bar = 0.5 µm.
(D) Total area of mitochondria per 20 µm² of myofiber from tibialis anterior muscle of SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at asymptomatic (4 months), symptomatic (12 months), and end-stage of disease (13–14 months). Data are presented as mean ± SEM.

(A) Fatigue index of hindlimb muscles from SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals throughout disease. Fatigue index was quantified as the period (in seconds) of high-frequency electrical stimulation required to obtain a 50% decrease in muscle contraction. Data are presented as mean ± SEM. See also Figure S2.
(B) Treadmill performance (total distance and run time on the treadmill determined until exhaustion) of SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at the symptomatic stage of disease. Data are presented as mean ± SEM.
(C) Running wheel performance of SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at the symptomatic stage of disease. Total distance and run time on the wheel were determined during a 5 min testing period. Average speed corresponds to the mean speed of running during the mobile period. Data are presented as mean ± SEM.
(D) Open field performance of SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at the symptomatic stage of disease. Total distance covered and the time mobile were determined during a 60 min of tracking period. Average speed corresponds to the mean speed of movement during the mobile period. Data are presented as mean ± SEM.

(A) Representative hematoxylin and eosin stainings of the gastrocnemius muscle in asymptomatic and symptomatic SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals. The inset indicates clusters of small angular degenerating fibers.
(B) Quantification of average fiber area from hematoxylin and eosin-stained gastrocnemius muscle from SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals throughout disease. Data are presented as mean ± SEM. See also Figure S3.
(C) Relative mRNA expression levels of muscular degeneration markers MuRF-1 and cathepsin L in gastrocnemius muscle isolated from asymptomatic and symptomatic mutant SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals. mRNA expression was evaluated by quantitative real-time PCR. Data are presented as mean ± SEM.
(D) Levels of ADP-stimulated mitochondrial oxygen consumption in mitochondria isolated from the gastrocnemius muscle of symptomatic mutant SOD1^G37R and SOD1^G37R/MCK-PGC-1α and age-matched nontransgenic and MCK-PGC-1α animals oxidizing pyruvate and malate. In coupled mitochondrial respiration, oxygen consumption is directly proportional to the amount of ATP synthesized. Data are presented as mean ± SEM.

(A) Plot of ages (in days) at which disease onset (as determined by the weight peak; at onset, animals do not display any obvious motor phenotype), symptomatic stage (as determined by 10% weight loss from onset, a stage characterized by clear gait abnormalities and tremor) and end-stage (as determined by hindlimb paralysis and inability to right itself) were reached for SOD1^G37R (red) and SOD1^G37R/MCK-PGC-1α (blue) animals.
(B–D) Quantification of innervation at the neuromuscular junction of the gastrocnemius muscle (B), total number of α-motor axons in the lumbar L5 motor root (C), and quantification at disease end-stage of the average number of large cholinergic ventral horn motor neurons per section of lumbar spinal cord from SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals (D). Data are presented as mean ± SEM. See also Figure S4 for representative sections of the spinal cords used for quantification.
(E) Representative micrographs of lumbar spinal cord sections from SOD1^G37R and SOD1^G37R/MCK-PGC-1α animals at disease end-stage processed for immunofluorescence using antibodies detecting activated astrocytes (GFAP) or microglia (IbaI). Dashed outlines correspond to the boundary between gray and white matter.