Compartmentalization in cardiomyocytes modulates creatine kinase and adenylate kinase activities
Rikke Birkedal, Jelena Branovets, Marko Vendelin
FEBS Lett, 2024 Nov; 598(21): 2623-2640.
- PMID: 39112921
- DOI: 10.1002/1873-3468.14994
Significance
Heart muscle cells contain densely packed structures that restrict molecular movement and create local chemical environments. This published paper explains why these compartments matter for energy metabolism: local ATP, ADP, and AMP levels can alter the activity of creatine kinase and adenylate kinase, enzymes that help supply energy for contraction. Such effects may also influence cellular energy signaling, including AMP-activated kinase. Accounting for local rather than average metabolite concentrations will improve interpretation of cardiac physiology and help guide methods for measuring energy metabolism inside cells.
Abstract
Intracellular molecules are transported by motor proteins or move by diffusion resulting from random molecular motion. Cardiomyocytes are packed with structures that are crucial for function, but also confine the diffusional spaces, providing cells with a means to control diffusion. They form compartments in which local concentrations are different from the overall, average concentrations. For example, calcium and cyclic AMP are highly compartmentalized, allowing these versatile second messengers to send different signals depending on their location. In energetic compartmentalization, the ratios of AMP and ADP to ATP are different from the average ratios. This is important for the performance of ATPases fuelling cardiac excitation-contraction coupling and mechanical work. A recent study suggested that compartmentalization modulates the activity of creatine kinase and adenylate kinase in situ. This could have implications for energetic signaling through, for example, AMP-activated kinase. It highlights the importance of taking compartmentalization into account in our interpretation of cellular physiology and developing methods to assess local concentrations of AMP and ADP to enhance our understanding of compartmentalization in different cell types.
Keywords: adenylate kinase; cardiomyocytes; compartmentalization; creatine kinase; diffusion; signaling.