Fig. 3

Schematic diagram of the response to oxidative damage of the SERCA pump. Higher cytosolic oxidative stress irreversibly oxidizes the Cys674 residue of SERCA (step (1)) resulting in a reduced SERCA activity. The reduced SERCA activity increases the cytosolic Ca²⁺ concentration (step (2)). The high cytosolic [Ca²⁺] is detrimental to E-C coupling (step (3)) and eventually induces the decline in muscle force (step (4)). High cytosolic [Ca²⁺] also results in the impairment of mitochondrial Ca²⁺ homeostasis (step (5)), which leads to increased generation and release of mtROS to the cytosol (step (6)), and the elevated mtROS will trigger additional oxidation of SERCA (step (1)) exacerbating the damage elicited by oxidative stress