Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology

AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis, integrating metabolic, mitochondrial, and oxidative stress responses. In the heart, an organ with high and dynamically fluctuating energy demands, AMPK is essential for maintaining metabolic balance, particularly during conditions such as exercise, ischemia, hypertrophy, and heart failure. The AMPK complex comprises a catalytic α subunit and regulatory β and γ subunits, each with multiple isoforms (α1, α2; β1, β2; γ1, γ2, γ3) that confer tissue-specific distribution and functional specialization. This review highlights the isoform-specific roles of AMPK in the heart, emphasizing their distinct contributions to myocardial energy metabolism, contractile function, and cardiac remodeling across diverse physiological and pathological conditions.