Fig. 9.

Schematic diagram exhibiting possible involvement of FBXL4 in HFpEF-associated cardiomyopathy through FBXL4-evoked Drp1 degradation in a proteasomal-dependent manner. HFpEF downregulates FBXL4 level, resulting hyperactivation of Drp1 and subsequent mitochondrial injury. Elevated FBXL4 level rescues against HFpEF-induced cardiac remodeling, diastolic dysfunction, and mitochondrial injury (mitochondrial fragmentation, collapsed membrane potential and intracellular Ca²⁺ overload due to defective SERCA2a function) through reverting hyperactivation of Drp1-mediated mitochondrial fission.