VITAMIN C-DEPENDENT REDUCTION OF FERRI-CYTOCHROME C IN FULLY INTACT MITOCHONDRIA LEADS TO SUPEROXIDE GENERATION VIA A REVERSE ELECTRON FLOW
LISA RICHARDA KREMER *
Institute of Physiological Chemistry, Universitätsklinikum Essen, Hufelandstraße 55, 45127 Essen, Germany.
JULIA LAUDIEN
Institute of Physiological Chemistry, Universitätsklinikum Essen, Hufelandstraße 55, 45127 Essen, Germany.
UTA KERKWEG
Institute of Physiological Chemistry, Universitätsklinikum Essen, Hufelandstraße 55, 45127 Essen, Germany.
MICHAEL KIRSCH
Institute of Physiological Chemistry, Universitätsklinikum Essen, Hufelandstraße 55, 45127 Essen, Germany.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: Vitamin C, cytochrome c reduction, superoxide anions, mitochondria, reverse electron flow