Key Points
- This research aims to explore how the creatine/phosphocreatine system regulates mitochondrial respiration in cardiac muscle cells.
- Experimental studies on permeabilized heart fibers of mice
- In silico computer modeling of metabolic regulation
- Analysis of the relationship between metabolite levels and mitochondrial respiration
- At low to moderate workloads (VO2 up to 70 micromol min-1 g-1 dry weight), respiration is mainly influenced by inorganic phosphate levels.
- At higher workloads, respiration primarily depends on creatine and phosphocreatine concentrations, as well as time-averaged ADP levels.
- Inhibition of creatine kinase necessitates high ADP levels for effective mitochondrial respiration, which can impede muscle contraction.
Structured PICO
PPopulationPermeabilized heart fibres of mice and computer modelling in silico
IInterventionEvaluation of the creatine/phosphocreatine system and compartmentalized energy transfer
OOutcomeRate of mitochondrial respiration and its regulatory factors (inorganic phosphate, creatine, phosphocreatine, ADP)surrogate
The study demonstrates that multiple parallel regulatory factors, including inorganic phosphate, creatine, phosphocreatine, and ADP, control the rate of mitochondrial oxygen consumption depending on the workload in cardiac muscle cells.