Guzun 2015 Acta Physiol (Oxf)

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Guzun R, Kaambre T, Bagur R, Grichine A, Usson Y, Varikmaa M, Anmann T, Tepp K, Timohhina N, Shevchuk I, Chekulayev V, Boucher F, Dos Santos P, Schlattner U, Wallimann T, Kuznetsov AV, Dzeja P, Aliev M, Saks V (2015) Modular organization of cardiac energy metabolism:energy conversion, transfer and feedback regulation. Acta Physiol (Oxf) 213:84-106.

» PMID: 24666671 Open Access

Guzun R, Kaambre T, Bagur R, Grichine A, Usson Y, Varikmaa M, Anmann T, Tepp K, Timohhina N, Shevchuk I, Chekulayev V, Boucher F, Dos Santos P, Schlattner U, Wallimann T, Kuznetsov AV, Dzeja P, Aliev M, Saks V (2015) Acta Physiol (Oxf)

Abstract: To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of Intra-Cellular 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 key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (mtOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and micro-compartmentalization. Based on the experimental and theoretical (mathematical modeling) 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 mtOM 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 homeostasis.

Keywords: Cardiac metabolism, Mitochondria, Respiration regulation, Creatine kinase

O2k-Network Lab: EE Tallinn Kaambre T, EE Tallinn Saks VA, FR Pessac Diolez P, FR Grenoble Schlattner U, FR Grenoble Saks VA, CH Zurich Wallimann T


Labels: MiParea: Respiration 


Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized cells, Isolated mitochondria  Enzyme: Adenine nucleotide translocase, Inner mt-membrane transporter, Supercomplex  Regulation: ADP, ATP production, PCr;Cr  Coupling state: OXPHOS  Pathway:HRR: Oxygraph-2k 

Review