Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are 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 cross-over design, 8 physically active males completed three experimental trials of concurrent exercise with either post-exercise 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 post-exercise. Select autophagy-related gene (Atg) proteins decreased compared to 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, NRF-1) and translational (COXIV, ATPAF1, 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.