Bioenergetic Feedback between Heart Cell Contractile Machinery and Mitochondrial 3D Deformations

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Abstract

In the heart, mitochondria are arranged in pairs sandwiched between the contractile machinery, which is the major ATP consumer. Thus, in response to the contraction-relaxation cycle of the cell, the mitochondrial membrane should deform accordingly. Membrane deformations in isolated ATP synthesis or in isolated mitochondria affect ATP production. However, it is unknown whether physiological deformation of the mitochondrial membrane in response to the contraction-relaxation cycle can act as a bioenergetic signaling mechanism between ATP demand to supply. We used both experimental and computational tools to reveal whether bioenergetic feedback exists between heart cell contractile machinery and mitochondrial three-dimensional (3D) deformations. We measured the mitochondrial 3D deformation in contracting rabbit cardiac myocytes and used published data on rat cardiac myocytes. These measurements were an input to a novel biophysics model that includes a description of ionic molecules on the mitochondrial membrane, Ca2+ cycling, and mitochondrial membrane stress. As is the case for rat cardiomyocytes, in rabbit cardiomyocytes, the mitochondrial length contracted and expanded with a similar dynamic as the sarcomere length. In contrast, the mitochondrial width expanded and then contracted with a similar dynamic as the mitochondrial length. Differences in the extent of deformation and fractional deformation between the width- and thick-axes were quantified and interpreted as the degree anisotropy between those respective axes. Finally, the model predicts that significant bioenergetic feedback between heart cell contractile machinery and mitochondrial 3D deformations does exist in unloaded rabbit and rat cells. However, this feedback is not a dominant mechanism in ATP supply to demand matching.

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Kamoun, D., Behar, J., Leichner, J. M., & Yaniv, Y. (2018). Bioenergetic Feedback between Heart Cell Contractile Machinery and Mitochondrial 3D Deformations. Biophysical Journal, 115(8), 1603–1613. https://doi.org/10.1016/j.bpj.2018.08.039

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