title: Mitochondrial colocalization with Ca2+ release sites is crucial to cardiac metabolism.
abstract: In cardiomyocyte subcellular structures, colocalization of mitochondria with Ca2+ release sites is implicated in regulation of cardiac energetics by facilitating Ca2+ influx into mitochondria to modulate the tricarboxylic acid (TCA) cycle. However, current experimental techniques limit detailed examination of this regulatory mechanism. Earlier, we developed a three-dimensional (3D) finite-element cardiomyocyte model featuring a subcellular structure that integrates excitation-contraction coupling and energy metabolism. Here, using this model, we examined the influence of distance between mitochondria and Ca2+ release sites by comparing a normal (50-nm) distance model and a large (200-nm) distance model (LD). The influence of distance was minimal under a low pacing rate (0.25 Hz), but under a higher pacing rate (2 Hz), lower levels of mitochondrial Ca2+ and NADH, elevated phosphate, and suppressed force generation became apparent in the LD model. Such differences became greater when functional impairments (reduced TCA cycle activity, uncoupling effect, and failing excitation-contraction coupling) were additionally imposed. We concluded that juxtaposition of the mitochondria and the Ca2+ release sites is crucial for rapid signal transmission to maintain cardiac-energy balance. The idealized 3D model of cardiac excitation-contraction and metabolism is a powerful tool to study cardiac energetics.
authors: Department of Frontier Science, The University of Tokyo, Kashiwa, Chiba, Japan. asuka-h@sml.k.u-tokyo.ac.jp
authors: Asuka
authors: A
authors: Hatano
authors: Jun-ichi
authors: J
authors: Okada
authors: Takumi
authors: T
authors: Washio
authors: Toshiaki
authors: T
authors: Hisada
authors: Seiryo
authors: S
authors: Sugiura
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D013997:Time Factors
chemical_list: D000205:Actomyosin; D000251:Adenosine Triphosphatases; D002118:Calcium