Mitochondrial semi-autonomous inheritance in cardiovascular pathology: Emerging mechanisms and therapeutic opportunities

Cardiovascular diseases (CVDs) continue to be a leading contributor to morbidity and mortality worldwide, with mitochondrial dysfunction emerging as a key pathological hallmark. As semi-autonomous organelles, mitochondria regulate cellular energy metabolism and homeostasis through intricate interactions between nuclear and mitochondrial genomes. This review synthesizes recent advances in understanding mitochondrial semi-autonomous inheritance mechanisms in cardiac pathology, encompassing mtDNA dynamics, epigenetic and non-epigenetic modifications, mtDNA release-induced inflammation, and mito-nuclear communication. Impaired regulation of the aforementioned processes causes disruption to the mitochondrial function, inducing cardiac remodeling and CVD progression. Here, we reveal novel therapeutic opportunities, including natural and pharmaceutical modulators, mitochondrial gene-editing technologies, and ncRNA-based interventions which can potentially restore mitochondrial homeostasis. Moreover, several challenges such as achieving precise drug targeting and implementation of real-time efficacy monitoring remain to be resolved. Future research should develop strategies to close these gaps, identify the context-dependent mechanisms, and advance translational applications to improve the prognosis of CVDs.