Key result
Cardiomyocyte structural modules restrict ATP diffusion for fast local transfer, potentially disrupted in failing hearts.
Understanding the modular structural design of cardiomyocytes provides insights into intracellular energy transfer mechanisms and potential pathophysiological disruptions in heart failure.
May suggest energy transfer disruption as a target in heart failure; leaves open causal role and need for validation.
The ontogeny of the heart describes its development from the fetal to the adult stage. In newborn mammals, blood pressure and thus cardiac performance are relatively low. The cardiomyocytes are thin, and with a central core of mitochondria surrounded by a ring of myofilaments, while the sarcoplasmic reticulum (SR) is sparse. During development, as blood pressure and performance increase, the cardiomyocytes become more packed with structures involved in excitation-contraction (e-c) coupling (SR and myofilaments) and the generation of ATP (mitochondria) to fuel the contraction. In parallel, the e-c coupling relies increasingly on calcium fluxes through the SR, while metabolism relies increasingly on fatty acid oxidation. The development of transverse tubules and SR brings channels and transporters interacting via calcium closer to each other and is crucial for e-c coupling. However, for energy transfer, it may seem counterintuitive that the increased structural density restricts the overall ATP/ADP diffusion. In this review, we discuss how this is because of the organization of all these structures forming modules. Although the overall diffusion across modules is more restricted, the energy transfer within modules is fast. A few studies suggest that in failing hearts this modular design is disrupted, and this may compromise intracellular energy transfer. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.
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Birkedal et al. (2022) conducted a review in Cardiomyocyte ontogeny and metabolism. Cardiomyocyte development and structural modularity was evaluated. Cardiomyocyte structural modules restrict overall ATP/ADP diffusion but enable fast energy transfer within modules, a design that may be disrupted in failing hearts.
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