title: Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation.
abstract: To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure-function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis.
authors.affiliation: Laboratory of Fundamental and Applied Bioenergetics, INSERM U1055, Joseph Fourier University, Grenoble, France; Department of Rehabilitation and Physiology, University Hospital, Grenoble, France.
authors.forename: R
authors.initials: R
authors.lastname: Guzun
authors.forename: T
authors.initials: T
authors.lastname: Kaambre
authors.forename: R
authors.initials: R
authors.lastname: Bagur
authors.forename: A
authors.initials: A
authors.lastname: Grichine
authors.forename: Y
authors.initials: Y
authors.lastname: Usson
authors.forename: M
authors.initials: M
authors.lastname: Varikmaa
authors.forename: T
authors.initials: T
authors.lastname: Anmann
authors.forename: K
authors.initials: K
authors.lastname: Tepp
authors.forename: N
authors.initials: N
authors.lastname: Timohhina
authors.forename: I
authors.initials: I
authors.lastname: Shevchuk
authors.forename: V
authors.initials: V
authors.lastname: Chekulayev
authors.forename: F
authors.initials: F
authors.lastname: Boucher
authors.forename: P
authors.initials: P
authors.lastname: Dos Santos
authors.forename: U
authors.initials: U
authors.lastname: Schlattner
authors.forename: T
authors.initials: T
authors.lastname: Wallimann
authors.forename: A V
authors.initials: AV
authors.lastname: Kuznetsov
authors.forename: P
authors.initials: P
authors.lastname: Dzeja
authors.forename: M
authors.initials: M
authors.lastname: Aliev
authors.forename: V
authors.initials: V
authors.lastname: Saks
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology
keywords: cardiac metabolism; creatine kinase; mitochondria; respiration regulation