Four hypotheses on mitochondria’s role in the development and regulation of oxidative stress in the normal state, cell pathology and reversion of tumor cells

SummaryThe biological evolution has resulted in adaptation of both unicellular and multicellular organisms to negative effect of excessive O2 in reply to gradual increase of free oxygen (O2) contents in the earth atmosphere. This adaptation has led to formation of various antioxidant systems in the organism. Such system within the cell has hierarchic structure and is represented by at least than three levels of protection: antioxygene, antiradical and antiperoxide. The first and most effective antioxidant level is represented as mitochondrial respiration able to perform several functions. One of these functions is antioxygene since the very the mitochondria’s capability to be a main O2 consumer in the cell provides for low but sufficient for respiration and energy supply levels of O2 partial pressure and dependent concentrations of active O2 forms. The latters, being signal molecules at certain values, modify regular and synthetic processes in the cells either directly or indirectly. This is the possibility for mitochondria to more extensively affect the intracellular processes than simply produce ATP. In case of defective of the cell first protection line the hyperoxia starts due to poor utilization of the incoming O2. Change in mitochondria’s “capacity” (quantity, size and maturity level of mitochondria) anyway occurring in the cells are an efficient way of regulation of the oxy-peroxide condition (oxidative stress) and related signal channels. The relationship between changes in the condition of cells, i.e. from their normal state to different pathologic forms, and growing disbalance Δ(PO–AO) between its pro-oxygen (PO) and anti-oxygen (AO) components has been assumed. It is expected that during the evolution the cell could have supposedly acquired a sequence of “specialized” Δ(PO–AO) disbalances. Each sequence needs to implement a certain set of biochemical processes. The probability of Δ(PO–AO) disbalance gradation with specification of their value ranges has been determined. These ranges identify or impact certain cell state, namely proliferation of normal cell (oxidative mitogenesis), ageing, A1 apoptosis, carcinogenesis, A2 apoptosis, and oxidative cytolysis. The cited assumption allows us to: (1) explain reverse dependence of cell proliferation due to the level of their differentiation, increase in the amount and activity of mitochondria as an indispensable condition for the disbalance shift towards differentiation, (2) bring up the idea that regress of the cells, and in particular tumour cells, directly results from the Δ(PO–AO) disbalance decrease to certain levels under the influence of reverse inductors, (3) explain relatively easy and frequent embryonic and stem cells malignancy, and also their reversal normalization. These phenomena occur due to small number and/or size of mitochondria in the designated cells. To verify the abovementioned hypotheses it is primarily necessary to be able to stimulate and slow down the mitochondria biogenesis in the embryonic, stem, ageing, cancer and other cells.