Researchers at the University of Liverpool and University of Oxford discovered that lysosomes, cell structures known for recycling waste, also regulate heart rhythm by acting as signaling centers. The team published their findings in Cardiovascular Research.
Lysosomes help the heart's natural pacemaker respond to stimulation that increases heart rate, the researchers found. They communicate through a signaling pathway involving cAMP, a messenger molecule that accelerates heart rate. This represents the first demonstration that lysosomal calcium signaling can trigger cAMP production in heart cells, rather than simply strengthening existing calcium signals.
The researchers combined animal studies with experiments using laboratory-grown human heart cells and human cardiac tissue from mice, guinea pigs, rats and goats. They identified two proteins, CaMKII and AC1, as likely components of this pathway. AC1 was located near lysosomes within heart cells, suggesting that lysosome-derived calcium signals may be rapidly relayed to systems controlling heart rhythm.
Rebecca-Ann Burton, associate professor at the University of Liverpool and senior corresponding author, stated, "This is the first study to show that lysosomal calcium signaling can trigger the production of cAMP in heart cells, rather than simply strengthening existing calcium signals."
The team also investigated lysosomes in atrial fibrillation, the most common heart rhythm disorder. In both animal models and human tissue samples with atrial fibrillation, lysosomes were larger and showed altered spatial relationships with other cellular structures compared with normal tissue. The researchers identified changes in proteins linked to lysosomal function and autophagy, the process by which cells break down and recycle damaged components. Further studies are needed to determine how these alterations contribute to the disease's development or progression.