NOX4 and ischemia: Accordingly, Sciarretta et al. [25] demonstrated that during fasting and prolonged ischemia, NOX4 was activated in the mouse heart, and that cardiac-specific NOX4-knockout mice exposed to energy stress exhibited increased infarct size and myocardial necrosis, and decreased LV contractile function, myocardial ATP content and autophagy activation, suggesting that cardiac NOX4 critically mediates autophagy in response to energy stress to ensure cardioprotection (Table 2).