Korzeniewski 2013 Abstract MiP2013

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Korzeniewski B (2013) Regulation of oxidative phosphorylation during work transitions in different tissues results from its kinetic properties. Mitochondr Physiol Network 18.08.


Bernard Korzeniewski

MiP2013, Book of Abstracts Open Access

Korzeniewski B (2013)

Event: MiPNet18.08_MiP2013

The regulation of oxidative phosphorylation (OXPHOS) during work transitions in skeletal muscle, heart and other tissues is still not well understood. Different computer models of this process have been developed that are characterized by various kinetic properties. In the present theoretical study it is shown that models belonging to one group [1-3], which assume an approximately uniform distribution of metabolic control over oxygen consumption (JO2) among particular oxidative phosphorylation complexes, C (CI, CIII, CIV, ATP synthase, ATP/ADP carrier, phosphate carrier), predict that all OXPHOS complexes are directly activated in parallel with ATP usage and NADH supply by some external cytosolic factor/mechanism during low-to-high work transitions in skeletal muscle and heart (‘each-step-activation’ mechanism) [1,3,4]. A direct activation during work transitions of the ATP supply block in general was first proposed in relation to skeletal muscle by Peter Hochachka [5,6]. Models belonging to another group [6,7], which assume that among OXPHOS complexes CIII keeps almost all of the metabolic control over JO2 (the control of other complexes is close to zero) and that it is strongly activated by inorganic phosphate (Pi), predict that an increase in Pi is the main mechanism responsible for OXPHOS activation (feedback-activation mechanism) [7,8]. It is demonstrated that computer models based on the each-step activation mechanism reproduce experimental data much better than models assuming the feedback-activation mechanism. Experimental studies revealed an approximately equal distribution of control over JO2 among OXPHOS complexes. They predict that different each-step activation intensities generate different (slopes of) the JO2/[ADP] relationships encountered in different muscles. These models enable a good homeostasis of not only ADP and PCr, but also of Pi and NADH during large increases in JO2. Finally, they do not imply a very high value of proton leak at low work in heart and at rest in skeletal muscle.

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 

Tissue;cell: Heart, Skeletal muscle 

Regulation: ADP, Flux control, Phosphate, Redox state  Coupling state: LEAK, OXPHOS 


Affiliations and author contributions

Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. - Email: bernard.korzeniewski@gmail.com


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  2. Korzeniewski B, Zoladz JA (2001) A model of oxidative phosphorylation in mammalian skeletal muscle. Biophys Chem 92: 17-34.
  3. Korzeniewski B (2006) Oxygen consumption and metabolite concentrations during transitions between different work intensities in heart. Am J Physiol 291: H1466-H1471.
  4. Korzeniewski B (2007) Regulation of oxidative phosphorylation through parallel activation. Biophys Chem 129: 93-110.
  5. Hochachka PW, Matheson GO (1992) Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscle. J Appl Physiol 73: 1697-1703.
  6. Hochachka P (1994) Muscles as metabolic machines. CRC Press, Boca Raton.
  7. Beard DA (2006) Modeling of oxygen transport and cellular energetics explains observations on in vivo cardiac energy metabolism. PloS Comp Biol 2: 1093-1106.
  8. Wu F, Jeneson JAL, Beard DA (2007) Oxidative ATP synthesis in skeletal muscle is controlled by substrate feedback. Am J Physiol 292: C115-C124.