VITAMIN C-DEPENDENT REDUCTION OF FERRI-CYTOCHROME C IN FULLY INTACT MITOCHONDRIA LEADS TO SUPEROXIDE GENERATION VIA A REVERSE ELECTRON FLOW

Mitochondria produce adenosine-5´-triphosphate (ATP) by an oxidative phosphorylation system (OXPHOS) with NADH and FADH2 as reducing entities.

In contrast, the well-known reducing agent vitamin C is not reported as being an electron donor to the OXPHOS and is only known to reduce ferri-cytochrome c in test tube experiments.

In this manuscript a vitamin C-dependent reduction of mitochondrial ferri-cytochrome c is demonstrated in isolated, fully intact rat mitochondria with UV-vis spectroscopy in reflection. Since the thermodynamic potential of complex IV is much higher than that of complex II, a reverse electron flow from ferrous-cytochrome c to complex II is feasible, at least in experimental systems. Consequently, the increased mitochondrial oxygen consumption after vitamin C application accelerated generation of the intermediate superoxide at complex II and failed in producing ATP. However, in illnesses with a disrupted complex III, where a reverse electron flow is impossible, the pharmacological discard application of vitamin C might be a therapeutic option.