Controled oxidation in living systems
Stéphanie Bonneau (Laboratoire Jean Perrin, Paris)
Living systems produce energy by oxidizing carbon : in aerobic organisms, a major step of this oxidation is processed by the respiratory chain in mitochondria. Energy production involves oxidation and subsequent ageing of the cellular materials. The control of their oxidative activity allows cells to remain far enough to the thermodynamic equilibrium and consequently the balance between respiration and ageing is a major regulation parameter of cell’s fate. The key role of mitochondria in this phenomenon will be discussed.
Experimentally, the control of the cellular oxidation is performed by using chosen photosensitizers. Due to their macrocycle, such molecules present very special photo-physical properties. Their light irradiation generates, through their triplet state, reactive oxygen species. The lifetime of these molecular species is very short and their action is very localized. To specifically target photosensitizers to one or the other cell compartments is thus the basis of their potential to modify and control the physiology of the cells. For example, the photo-chemical internalization (PCI) of macromolecules into cells is based on the photo-induced alteration of endosomal membranes – before their maturation in lysosomes – allowing the escape of the macromolecules, free to reach its targets within cell. More extensive photo-induced changes, in particular to the mitochondria, lead to cell death by necrosis or apoptosis. This photo-induced cell death is basis of an anticancer therapy so-called PDT.
First, we focussed on the photo-induced modifications of the cellular trafficking. By combining measurements of local cytoplasmic viscosity and active trafficking, we found that photodynamic effect induced a only slight increase in viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation. Secondly, to better apprehend such complex effects, we turned to model systems. In particular, we focused on photo-oxidation of membranes lipids, that are important oxidative targets. We extensively studied their modifications under photo-oxidation. Our purpose is to demonstrate that the photo-induced permeabilization of the membranes is correlated with a deep physical stress, which can be relaxed by various pathways, depending on its lipids composition, which is characteristic of the targeted cellular compartment.