PMID- 27522222 OWN - NLM STAT- MEDLINE DCOM- 20171225 LR - 20181113 IS - 1432-136X (Electronic) IS - 0174-1578 (Linking) VI - 187 IP - 1 DP - 2017 Jan TI - Metabolic compartmentation in rainbow trout cardiomyocytes: coupling of hexokinase but not creatine kinase to mitochondrial respiration. PG - 103-116 LID - 10.1007/s00360-016-1025-x [doi] AB - Rainbow trout (Oncorhynchus mykiss) cardiomyocytes have a simple morphology with fewer membrane structures such as sarcoplasmic reticulum and t-tubules penetrating the cytosol. Despite this, intracellular ADP diffusion is restricted. Intriguingly, although diffusion is restricted, trout cardiomyocytes seem to lack the coupling between mitochondrial creatine kinase (CK) and respiration. Our aim was to study the distribution of diffusion restrictions in permeabilized trout cardiomyocytes and verify the role of CK. We found a high activity of hexokinase (HK), which led us to reassess the situation in trout cardiomyocytes. We show that diffusion restrictions are more prominent than previously thought. In the presence of a competitive ADP-trapping system, ADP produced by HK, but not CK, was channeled to the mitochondria. In agreement with this, we found no positively charged mitochondrial CK in trout heart homogenate. The results were best fit by a simple mathematical model suggesting that trout cardiomyocytes lack a functional coupling between ATPases and pyruvate kinase. The model simulations show that diffusion is restricted to almost the same extent in the cytosol and by the outer mitochondrial membrane. Furthermore, they confirm that HK, but not CK, is functionally coupled to respiration. In perspective, our results suggest that across a range of species, cardiomyocyte morphology and metabolism go hand in hand with cardiac performance, which is adapted to the circumstances. Mitochondrial CK is coupled to respiration in adult mammalian hearts, which are specialized to high, sustained performance. HK associates with mitochondria in hearts of trout and neonatal mammals, which are more hypoxia-tolerant. FAU - Karro, Niina AU - Karro N AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. FAU - Sepp, Mervi AU - Sepp M AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. FAU - Jugai, Svetlana AU - Jugai S AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. FAU - Laasmaa, Martin AU - Laasmaa M AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. FAU - Vendelin, Marko AU - Vendelin M AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. FAU - Birkedal, Rikke AU - Birkedal R AD - Institute of Cybernetics, Tallinn University of Technology, Akadeemia 21, 12618, Tallinn, Estonia. rikke@sysbio.ioc.ee. LA - eng PT - Journal Article DEP - 20160813 PL - Germany TA - J Comp Physiol B JT - Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology JID - 8413200 RN - EC 2.7.1.1 (Hexokinase) RN - EC 2.7.3.2 (Creatine Kinase) SB - IM MH - Animals MH - Cell Respiration MH - Creatine Kinase/metabolism MH - Hexokinase/*metabolism MH - Mitochondria, Heart/*metabolism MH - Models, Biological MH - Myocytes, Cardiac/*metabolism MH - Oncorhynchus mykiss/*metabolism MH - Oxygen Consumption OTO - NOTNLM OT - ADP diffusion restriction OT - Creatine kinase OT - Heart OT - Hexokinase OT - Metabolic compartmentation OT - Rainbow trout EDAT- 2016/08/16 06:00 MHDA- 2017/12/26 06:00 CRDT- 2016/08/15 06:00 PHST- 2015/09/24 00:00 [received] PHST- 2016/07/29 00:00 [accepted] PHST- 2016/07/22 00:00 [revised] PHST- 2016/08/16 06:00 [pubmed] PHST- 2017/12/26 06:00 [medline] PHST- 2016/08/15 06:00 [entrez] AID - 10.1007/s00360-016-1025-x [pii] AID - 10.1007/s00360-016-1025-x [doi] PST - ppublish SO - J Comp Physiol B. 2017 Jan;187(1):103-116. doi: 10.1007/s00360-016-1025-x. Epub 2016 Aug 13.