Abstract
We show that mitochondria from the kidney of mice (MKM), rat brain (RBM), and heart (RHM) oxidize long-chain fatty acids at high rates in all metabolic states only in the presence of any other mitochondrial metabolites: succinate, glutamate, or pyruvate. All supporting substrates increased several folds the respiration rates in State 4 and State 3. The stimulations of the State 3 respiration with palmitoyl-carnitine + malate oxidation (100%) were: with succinate in MKM 340%, RBM 370%, and RHM 340%; with glutamate - MKM 200%, RBM 270%, and RHM 270%; and with pyruvate - MKM 150%, RBM 260%, and RHM 280%. The increases in O2 consumption in State 4 were due to increased leakage of electrons to produce superoxide radicals (O2•). Earlier, we have shown that the brain and heart mitochondria possess a strong intrinsic inhibition of succinate oxidation to prevent the excessive O2• production at diminished functional loads. We show that kidney mitochondria lack the intrinsic inhibition of SDH. The new methodology to study β-oxidation of LCFAs opens the opportunity to study energy metabolism under normal and pathological conditions, particularly in the organs that utilize LCFAs as the main energy source.
Competing Interest Statement
The authors have declared no competing interest.
