Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets

Figures

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  Fig. 1.. This diagram illustrates how metabolic remodeling and mitochondrial stress play a pivotal role in the development of atrial fibrillation (AF), arising from systemic metabolic disorders. In response to metabolic stress, the atrial myocardium undergoes a metabolic shift characterized by alterations in lipid, glucose, and ketone metabolism. These changes, along with mitochondrial dysfunction, contribute to a pro-arrhythmic environment. Metabolic disturbances, in conjunction with structural and electrical remodeling, promote the abnormal electrical activity characteristic of AF. AGEs, advanced glycation end-products; DAGs, diacylglycerols; ROS, reactive oxygen species; mtDNA, mitochondrial DNA.

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  Fig. 2.. Pathophysiological drivers of mitochondrial dysfunction in atrial fibrillation. Mitochondrial dynamics—including fission, fusion, and mitophagy—are essential for maintaining mitochondrial function and cellular metabolism. An imbalance in these processes can lead to mitochondrial dysfunction, characterized by impaired energy production and increased oxidative stress. These alterations contribute to atrial arrhythmogenesis through mechanisms such as ion channel remodeling, inflammation, atrial fibrosis, disrupted mitochondrial–ER interactions, and impaired regulation of mitochondrial and cytosolic Ca2+ levels. Drp1, dynamin-related protein 1; Mff, mitochondrial fission factor; Mfn1, mitofusion-1; ATP, adenosine triphosphate; KATP, ATP-sensitive potassium channel; ER, endoplasmic reticulum; Ca2+, calcium.