Chronic Alcohol and Skeletal Muscle

Alcohol and Skeletal Muscle in Health and Disease

“…SKM mass is maintained by the balance of anabolic (protein synthesis) and catabolic (protein breakdown) signaling. Major anabolic stimuli—including amino acids, insulin, insulin-like growth factor 1 (IGF-1)—and mechanical loading promote protein synthesis by converging on the mechanistic/mammalian target of rapamycin (mTOR) signaling pathway (reviewed by Bourgeois et al 9 and Steiner et al 10 ). SKM protein breakdown occurs through activation of the ubiquitin proteasome pathway (UPP) and SKM-specific ubiquitin ligases or atrogenes; atrogin-1 (also known as muscle atrophy F-box, or MAFbx) and muscle RING-finger protein-1 (MuRF-1) are often used as markers of UPP activation.…”

“…Though most adult muscle growth is driven by hypertrophy of existing myofibers, muscle stem cells (satellite cells) contribute to myofiber regeneration, especially in response to injury or atrophy. 13 , 14 Finally, being highly dynamic and with high energy demands, SKM relies heavily on mitochondria for bioenergetic demands, redox balance, and programmed death signaling (reviewed by Bourgeois et al 9 ). Evidence suggests that alcohol significantly affects all these major attributes of SKM mass and function, as discussed in this review.…”

“…The second major protein breakdown pathway is activation of the autophagiclysosomal system that degrades misfolded proteins by formation of a phagophore followed by engulfing of degraded proteins. [9][10][11][12] Myofibers, their structural components, and the extracellular matrix intricately communicate to maintain SKM structure. Though most adult muscle growth is driven by hypertrophy of existing myofibers, muscle stem cells (satellite cells) contribute to myofiber regeneration, especially in response to injury or atrophy.…”