Respirasome Persistence Without Efficient Electron Channeling in Cardiac Mitochondria From an Animal Model of Hypertension

Cardiac mitochondrial dysfunction contributes to hypertensive remodeling, but whether respiratory supercomplex organization preserves electron transfer efficiency during disease progression remains unresolved. Here, we examined the structural and functional organization of the respiratory complexes in cardiac mitochondria from stroke-resistant and stroke-prone spontaneously hypertensive rats exposed to normal or Japanese diet regimens. In both models, supramolecular analyses revealed the persistence of N-respirasome and Q-respirasome assemblies, indicating that major respiratory supercomplex species are maintained during sustained hypertension and in the pre-stroke state. However, metabolic flux control analysis consistently showed that cytochrome c oxidase or Complex IV exerted only limited control over respiratory flux, with control coefficients below those expected for tightly channeled nicotinamide adenine dinucleotide (NADH)-dependent electron transfer. Thus, structural preservation of respirasomes was not matched by evidence of kinetically optimized coupling. These findings uncouple supercomplex detectability from functional electron channeling and suggest that, in the hypertensive heart, respiratory performance is constrained by qualitative defects in supercomplex organization rather than by their overt loss.