Tepp 2015 Abstract MiP2015

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Changes in energy transfer regulation during development and aging.

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Tepp K, Klepinin A, Timohhina N, Shevchuk I, Chekulayev V, Kaambre T (2015)

Event: MiP2015

In adult cardiomyocytes the main energy transfer pathway from mitochondria to the energy consumption sites is creatine kinase-phosphocreatine (CK-PCr) shuttle, while in the situation of high workload or pathology adenylate kinase (AK) and hexokinase (HK) pathways could compensate the energy requirements in some extent [1]. During postnatal period quick structural and functional changes in energy metabolism take place – rearrangement of mitochondria into regular pattern, distinctive for cardiomyocytes, and formation of Intracellular Energetic Unit (ICEU). The CK-PCr system activation is the last step of the formation of adult bioenergetic metabolism [2]. The alterations taking place in the energy transfer and kinetics of OXPHOS during healthy aging is till now have been less studied. In pathology of the heart the level of PCr have prognostic value in diagnosis [3]. Therefore, it is important to study the alteration of CK shuttle in aging as well as to find out the role of the alternative energy transfer systems.

The main methods used were confocal microscopy, high resolution respirometry with Oxygraph-2K, and real time quantitative PCR and western blot analysis. Results of the study showing that on the seventh postnatal day AMP activated mitochondrial respiration achieve the equal level with maximal OXPHOS capacity (with 2 mM ADP). During the same period mitochondrial CK activates. The adult energy metabolism has formed by the age of 3 month. In parallel isoforms levels of AK1 and AK3 increase significantly. HK expression profile changes from HK I, which is the main HK isoform in neonatal cardiomyocytes, to HK II that is predominant in the adult heart. These results demonstrate that the AK phosphotransfer system plays an important role in ATP turnover during CK system maturation.

In the aging cardiomyocytes gender related differences could be followed. Compared to adult the values of the apparent Michaelis-Menten constant Km(ADP) for 12- and 18-month male cardiac cells increases, as for females the value has even slightly decreased. At the same time creatine-stimulated respiration rate decreases in the cardiomyocytes of both sexes.

Results of the study allow to conclude that maturation of the ICEU is closely related to the formation of phosphocreatine/creatine kinase system that ensures the increasing energy demands. In developing cardiomyocytes AK pathway plays an important role in energy transfer till the CK-mediated phosphotransfer system is completely formed and functional. During aging the energy transfer regulation is influenced by gender differences and the CK phosphotransfer pathway efficiency is declined.


O2k-Network Lab: EE Tallinn Kaambre T


Labels: MiParea: Respiration  Pathology: Aging;senescence 


Tissue;cell: Heart 



HRR: Oxygraph-2k  Event: D1, Poster, P-flash  MiP2015 

Affiliations

1-Lab Bioenergetics, Nat Inst Chemical Physics Biophysics; 2-FSc, Dep Chemistry, Tallinn Univ Technology, Tallinn, Estonia. - kersti.tepp@kbfi.ee

References and acknowledgements

  1. Dzeja PP, Hoyer K, Tian R, Zhang S, Nemutlu E, Spindler M, Ingwall JS (2011) Rearrangement of energetic and substrate utilization networks compensate for chronic myocardial creatine kinase deficiency. J Physiol 589:5193-211
  2. Anmann T, Varikmaa M, Timohhina N, Tepp K, Shevchuk I, Chekulayev V, Saks V, Kaambre T (2014) Formation of highly organized intracellular structure and energy metabolism in cardiac muscle cells during postnatal development of rat heart. Biochimica et biophysica acta 1837:1350-61.
  3. Neubauer S (2007) The failing heart-an engine out of fuel. N Engl J Med 356: 1140-51.