Lysosomes, traditionally described as the cell’s recycling centers, also contribute to the regulation of heart rhythm, according to a study by researchers at the University of Liverpool, the University of Oxford and national and international collaborators. The findings were published in Cardiovascular Research.
The team found that lysosomes help heart cells respond to stimulation that normally accelerates the heartbeat. Their signaling involves calcium and cAMP, a messenger molecule associated with increases in heart rate. The researchers identified CaMKII and AC1 as likely components of this previously unrecognized pathway, with AC1 located close to lysosomes inside heart cells.
The study builds on earlier evidence that lysosomes can influence calcium signaling, but examines for the first time their role in controlling the heart’s natural pacemaker and heart rate. Researchers combined animal studies with experiments using laboratory-grown human heart cells and human cardiac tissue, drawing on findings from mice, guinea pigs, rats and goats.
The researchers also examined lysosomes in atrial fibrillation, a common heart rhythm disorder. In animal models and human tissue samples from atrial fibrillation, lysosomes were larger and showed altered spatial relationships with other cellular structures compared with tissue associated with sinus rhythm. The study also identified changes in proteins linked to lysosomal function and autophagy, the process cells use to break down and recycle damaged components.
Rebecca-Ann Burton, associate professor in the Department of Pharmacology and Therapeutics at the University of Liverpool and senior corresponding author, said the findings reveal a previously unrecognized connection between lysosomal calcium signaling and the pathways that regulate the heart’s pacemaker. She said the study shows that lysosomal calcium signaling can trigger cAMP production in heart cells and identifies a specific role for the pathway in cardiac pacemaking.
Niels Voigt, clinician-scientist and professor at Heidelberg University’s Medical Faculty Mannheim, said targeting lysosomal signaling could provide a new direction for investigating treatments for atrial fibrillation. Antony Galione, professor in the Department of Pharmacology at the University of Oxford, said the work highlights how lysosomes can deliver localized calcium signals that selectively regulate cellular processes.
The researchers said the findings point to structural remodeling in atrial heart muscle cells during atrial fibrillation, including changes in intracellular signaling domains and organelle organization. Further studies will be needed to establish how these alterations contribute to the development or progression of the disorder.
The study, titled “Lysosomal signalling pathways influence heart rhythm, and regulate atrial function,” was authored by Emily Akerman and colleagues and published in Cardiovascular Research in 2026. Its DOI is 10.1093/cvr/cvag207.
Sources: Phys.org.