Figure 1.

Theoretical graph of the transient and additive nature of reversible and irreversible redox PTMs in the context of skeletal muscle physiology and disease. (A) Acute oxidative insults (shaded area) can cause a swift and transient increase in reversible oxidative PTMs. Irreversible PTMs rely on protein degradation and turnover, while most reversible modifications can be cleared by the GSH/GSSG and Trx(red)/Trx(ox) redox couples. Subsequent acute oxidative insults can be deleterious if the modifications become irreversible, but this is not the case for reversible modifications, which, can cause transcriptional activation of the antioxidant response (adaptation, preconditioning, or hormesis) to suppress PTM formation. (B) Chronic oxidative insults can result in an oxidized redox status which persists throughout the duration of the stress. As with aging, many metabolic and functional skeletal muscle defects that result from this oxidized redox status can be rapidly reversed by restoring a more reduced redox environment. In contrast, irreversible oxidative modifications, however, can persist after the end of the oxidative insult.