Controlled power: how biology manages succinate-driven energy release

Oxidation of succinate by mitochondria can generate a higher protonmotive force (pmf) than can oxidation of NADH-linked substrates. Fundamentally, this is because of differences in redox potentials and gearing. Biology adds kinetic constraints that tune the oxidation of NADH and succinate to ensure that the resulting mitochondrial pmf is suitable for meeting cellular needs without triggering pathology. Tuning within an optimal range is used, for example, to shift ATP consumption between different consumers. Conditions that overcome these constraints and allow succinate oxidation to drive pmf too high can cause pathological generation of reactive oxygen species. We discuss the thermodynamic properties that allow succinate oxidation to drive pmf higher than NADH oxidation, and discuss the evidence for kinetic tuning of ATP production and for pathologies resulting from substantial succinate oxidation in vivo.

Automated summary

Mitochondrial oxidation of succinate can generate a higher protonmotive force than that of NADH-linked substrates, due to differences in redox potentials. Biological constraints tune the oxidation of NADH and succinate to maintain suitable mitochondrial pmf for cellular needs without causing pathology. Conditions that allow succinate oxidation to drive pmf too high can lead to pathological generation of reactive oxygen species.