FIG. 9.

Schematic diagram depicting possible mechanism(s) involved in paraquat- and AMPK deficiency (KD) induced changes in cardiac intracellular Ca²⁺ homeostasis and contractile function. Paraquat administration triggers activation of AMPK signaling. Activation of AMPK activates TSC complex (through phosphorylation) to enhance its inhibition on mTOR signaling and reduced phosphorylation of ULK1 at Ser⁷⁵⁷, leading to excessive autophagy and autophagy flux, which leads to cardiac dysfunction. AMPK can alternatively activate ULK1 at Ser⁷⁷⁷ to upregulate autophagy. AMPK deficiency suppresses autophagy via inhibition of AMPK/TSC/mTOR/ULK1⁷⁵⁷ and AMPK/ULK1⁷⁷⁷ signaling cascade en route to cardioprotection. Arrows indicate activation whereas the lines with a “T” ending denote inhibition. TSC, tuber sclerosis complex.