Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reduced 𝛼-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species

Figure 2

Schematic of the respiratory chain. The respiratory chain: in complex I, NADH is oxidized to NAD, while four protons are pumped from the mitochondrial matrix into the intermembrane space/cytosol. Concomitantly ubiquinon (Q), residing in the inner membranous space, is reduced to ubiquinol (QH₂) along with the uptake of two matrix protons. In Complex II, succinate is oxidized to fumarate while ubiquinon is reduced to ubiquinol. In this reduction two protons are taken up from the matrix space, but no protons are pumped across the mitochondrial membrane. In complex III, innermembranous ubiquinol is oxidized to ubiquinon. Via the q-cycle mechanism, two protons are taken up from the matrix space, and four protons are released into the inter membrane space/cytosol. The two electrons are consecutively transferred via Fe-S cluster to cytochrome c1 and reduce two molecules of cytochrome c. In complex IV, two molecules of reduced cytochrome c are oxidized, and oxygen is reduced to water along with the transduction of two protons from the matrix space into the inter membrane space/cytosol. With either NADH or succinate as substrates, the respiratory chain pumps ten and six protons, respectively, from the matrix space to the inter membrane space/cytosol, and one molecule of water is formed.