Cardiac adrenergic receptors and GRKs: mitochondrial modulation in the heart

The cellular 'powerhouse', mitochondria play vital roles in cardiac cells, including the modulation of contractility. Among the various mechanisms, the modulation of cardiac mitochondria by adrenergic signaling stands out as a crucial component in orchestrating cardiac function. Adrenergic system serving as the primary regulator of cardiac contractility, exerts its effects through alpha- and ss-adrenoceptors, which are regulated by G-protein-coupled receptor kinase 2 (GRK2) and ss-arrestin. In recent years, it has been revealed that these components of adrenergic signaling interact with mitochondria in diverse ways. alpha- and ss-adrenoceptors are reported to contribute to mitochondrial biogenesis, dynamics, and function. Besides, GRK2 is known to be localized to mitochondria, following oxidative stress or ischemic injury, and exerts negative metabolic effects. In this review, we outlined the contributions of these pivotal elements of adrenergic signaling to mitochondrial function. The better understanding of this delicate relationship holds crucial implications for novel therapeutic options to treat cardiovascular pathologies.