Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy

Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism( s ) ( e.g., increased protein breakdown ) underlying this observation is unknown. Autophagy is an intracellular “recycling” system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent ( combined resistance- and endurance-based ) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate ( 12 ± 2 standard drinks; ALC-CHO ), energy-matched alcohol and protein ( ALC-PRO ), or protein ( PRO ) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene ( Atg ) proteins decreased compared with rest with ALC-CHO ( P < 0.05 ) but not ALC-PRO. There were parallel increases ( P < 0.05 ) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy ( mitophagy ) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions ( P < 0.05 ); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only ( P < 0.05 ). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1α in ALC-PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional ( Tfam, SCO2, and NRF-1 ) and translational ( COX-IV, ATPAF1, and VDAC1 ) level ( P < 0.05 ). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis