Disrupted Calcium Interaction Linked to Atrial Fibrillation, Potential for Existing Drug Repurposing
New research from the University Medical Centre Göttingen (UMG) and the Würzburg University Hospital (UKW), led by Professors Niels Voigt and Christoph Maack, has identified a significant link between impaired communication between key cellular structures in the heart muscle and the progress of atrial fibrillation (AFib). The study, published in Circulation Research (October 2025, DOI: 10,1161/CIRCRESA.124,325588), points to a disruption in the interplay between mitochondria and the sarcoplasmic reticulum as a central mechanism driving the arrhythmia.
The research focuses on the vital roles of these two structures: mitochondria, responsible for cellular energy production, and the sarcoplasmic reticulum, a network within heart muscle cells that stores and releases calcium, triggering muscle contraction. Normally, these structures function in a tightly coupled manner, with mitochondria utilizing calcium signals from the sarcoplasmic reticulum to boost energy production, notably during periods of stress.
However, the team discovered that in patients with AFib, mitochondrial calcium uptake is reduced, hindering the regeneration of essential energy sources. Utilizing advanced imaging techniques - electron tomography and STED nanoscopy – researchers observed a loss of close spatial proximity between the sarcoplasmic reticulum and mitochondria in diseased heart cells. Electron tomography allowed for three-dimensional visualization of cell structures at the nanometer level, while STED nanoscopy provided significantly higher resolution imaging than conventional light microscopy. These techniques revealed that mitochondria in AFib patients lose their organized structure and detach from the sarcoplasmic reticulum, disrupting the heart’s energy balance.
Analysis of heart muscle samples from patients both with and without AFib, combined with biochemical measurements, confirmed these findings.
Interestingly, the study also revealed a potential therapeutic avenue. An existing,approved cholesterol-lowering drug demonstrated the ability to partially restore mitochondrial calcium absorption in heart muscle cells in vitro. Furthermore, analysis of patient data indicated a lower incidence of AFib among individuals taking this medication.
“Our results open up new perspectives for the treatment of atrial fibrillation,” stated Dr. Julius Pronto, postdoctoral researcher at the Institute of Pharmacology and Toxicology at UMG and lead author of the study. “If we succeed in specifically stabilizing the mitochondria and improving their calcium absorption, this could reduce the risk of cardiac arrhythmias in the long term.”
The research suggests that restoring calcium communication between the sarcoplasmic reticulum and mitochondria could be a key strategy in preventing and treating atrial fibrillation.
