Adrenergic Receptor Regulation of Mitochondrial Function in Cardiomyocytes

Abstract

Adrenergic receptors (ARs) are G protein-coupled receptors that are stimulated by catecholamines to induce a wide array of physiological effects across tissue types. Both a1and b-ARs are found on cardiomyocytes and regulate cardiac contractility and hypertrophy through diverse molecular pathways. Acute activation of cardiomyocyte b-ARs increases heart rate and contractility as an adaptive stress response. However, chronic b-AR stimulation contributes to the pathobiology of heart failure. By contrast, mounting evidence suggests that a1-ARs serve protective functions that may mitigate the deleterious effects of chronic b-AR activation.Here, we will review recent studies demonstrating that a1and b-ARs differentially regulate mitochondrial biogenesis and dynamics, mitochondrial calcium handling, and oxidative phosphorylation in cardiomyocytes. We will identify potential mechanisms of these actions and focus on the implications of these findings for the modulation of contractile function in the uninjured and failing heart. Collectively, we hope to elucidate important physiological processes through which these well-studied and clinically relevant receptors stimulate and fuel cardiac contraction to contribute to myocardial health and disease.

IFN‐γ and androgens disrupt mitochondrial function in murine myocytes

“…Finally, we provide proof of principle that effective treatment of cardiac stress with targeted beta‐blocking medication may offer a viable therapeutic option to potentially decrease cardiovascular death risk for SLE patients. Particularly, the specific use of beta‐adrenergic receptor 1 antagonists such as metoprolol could selectively protect the mitochondrial myocyte from high energy demands, improve the heart's response to stress, and limit heart damage [65]. Thus, our work highlights how androgens and IFN‐γ signatures reduce mitochondrial function in myocytes, limiting the heart's ability to cope with stress in autoimmunity.…”

Adrenergic Receptor Regulation of Mitochondrial Function in Cardiomyocytes: Erratum

“…In the September, 2022 issue of the Journal of Cardiovascular Pharmacology in the article by Sandroni et al, “Adrenergic Receptor Regulation of Mitochondrial Function in Cardiomyocytes,” 1 the numbered list of references provided for Table 1 is incorrect.…”

G Protein–Coupled Receptors—Receptors With New Tricks Up Their Sleeves

“…In this context, Jensen et al present a comprehensive summary of adrenergic receptor subtype regulation of mitochondrial biogenesis, focusing on the dynamics of mitochondrial fusion and fission, the regulation of mitochondrial calcium content, and the regulation of oxidative phosphorylation and reactive oxygen species (ROS) production. 9 The authors provide a detailed summary of the literature, which includes conflicting findings and highlights the many unresolved issues. As the authors note, future experiments involving genetic and molecular approaches designed to unravel divergent AR signaling responses in cardiac myocytes, with a focus on the mechanisms that might be time-specific or injury-specific, hold promise for the development of new pharmaceutical strategies.…”