It is known that full-length PGC-1α (FL-PGC-1a) in contrast to N-truncated (NT-PGC-1a) protein has a short half-life. Taking into consideration that the content of PGC-1a could influence further adaptive changes in muscle the aim of our study was to investigate the effect of ubiquitin-proteasome system activation after high intensity endurance exercises on PGC-1a content. Nine healthy endurance-trained (VO2max 61 ml/min/kg) subjects performed two continuous 70 min bicycle sessions on separate occasions: with low (L; 50% VO2max) and high (H; 70% VO2max) intensity . Before exercise, and 2 minutes, 4 and 8 hours after it biopsy samples from the m. vastus lateralis were taken under local anaesthesia (2 mL 2% lidocaine) by a microbiopsy technique. mRNA expression level, total and phosphorylated protein content were evaluated using q-PCR and Western blot. All data are normalized to reference gene or protein and submitted as median and interquartile range. The study was approved by the Human Ethics Committee of the Institute of Biomedical Problems (Moscow, Russia). Immediately after exercise increase in phosphorylation level of AMPK substrate – ACCSer79 in both sessions was observed (from 0.09(0.05-0.18) to 0.24(0.11-0.72) in L-session; from 0.08(0.04-0.30) to 0.52(0.19-1.06) in H-session). PGC-1a mRNA expression level after 4 hours of recovery also increased in a load-dependent manner (from 0.15(0.10-0.20) to 0.37(0.29-0.45) in L session; from 0.14(0.10-0.16) to 0,67(0.45-0.84) in H session). Phosphorylation of FOXO1Ser256 increased in L session immediately after the exrcise (from 1.31(0.81-2.10) to 1.46(1.08-3.50)), and decreased after 4 hours recovery (from 1.88(0.73-2.31) to 0.87(0.26-2.43)) in H session. MuRF1 expression decreased only immediately after L session (from 0.22(0.13-0.30) to 0.14(0.11-0.17)), whereas Atrogin-1 expression decreased in both groups: in L session after 8 hours from 1.38(0.87-1.83) to 0.67(0.61-1.45); and in H session after 4 hours from 1.38(0.77-1.68) to 0.80(0.70-0.90) and after 8 hours to 0.83(0.71-1.26)). Content of FL-PGC-1a was unchanged in L session, and had a tendency to decrease in H session immediately after the exercise (from 1.00(0.60-2.00) to 0.60(0.45-1.45); P=0.06). Whereas the content of NT-PGC-1a increased in L session (from 0.76(0.38-1.57) to 1.08(0.72-1.74)) and had a tendency to increase in H session (from 1.06(0.42-1.34) to 1.45(0.40-3.68), P=0.06). Thus the high intensity endurance exercise in comparison with the low intensity exercise results in ubiquitin-proteasome system activation. As the stability of FL-PGC-1a is low, this result may indicate that its content decreases after high intensity endurance exercise. This work was supported by the Russian Science Foundation (grant 14-15-00768).