Extraordinary Biomed Seminar: Mitochondrial Plasticity and Metabolic Rewiring in Cardiovascular Disease

  
Mitochondrial plasticity is a central determinant of cardiometabolic homeostasis and cardiovascular disease progression. Beyond their role in energy production, mitochondria dynamically adapt their morphology and function to regulate lipid handling, metabolic flexibility, and cellular stress responses. Experimental modulation of mitochondrial fusion demonstrates that systemic OPA1 overexpression promotes dyslipidemia and accelerates atherosclerosis in LDL receptor–deficient mice, linking organelle dynamics to vascular disease. Conversely, inhibition of inner mitochondrial fusion in hepatocytes mitigates metabolic-dysfunction associated liver disease and improves systemic metabolic parameters by altering bile acid conjugation. In the heart, mitochondrial remodeling critically governs lipid utilization and energetic efficiency, while PCSK9 deficiency induces metabolic rewiring that predisposes to heart failure with preserved ejection fraction. Together, these findings position mitochondrial dynamics as an integrative metabolic switch connecting hepatic lipid metabolism, circulating lipoproteins, and cardiac function. Targeting mitochondrial plasticity may therefore offer novel therapeutic strategies to modulate cardiometabolic risk and heart failure progression.