The Function and Supramolecular Assembly of the Mitochondrial Respiratory Complexes Underlie Hypertension-Related Stroke Susceptibility in a Model of Complex Human Disease

The role of mitochondrial dysfunction underlying increased susceptibility to cerebrovascular disease in hypertension, previously detected in stroke-prone spontaneously hypertensive rats (SHR-SP) fed with a high-salt stroke-permissive Japanese-style diet (JD), was studied for the first time at the molecular level. The Complex I (CI) (dis)assembly in the supramolecular organization of respiratory supercomplexes (SCs) has emerged as the main component impairing the kinetic activity and SCs organization of mitochondrial respiration in SHR-SP compared with the SHR-stroke resistant (SR) strain upon the same dietary condition. The leak of substrate channeling and SCs arrangement in CI-dependent NADH oxidation in JD-fed SHR-SP was not detected in SHR-SR upon the same dietary regimen. Our results highlight that SCs association linked to CI dynamic and stability protects from stroke manifestation.