Fig. 2

The effect of hypoxia on mitochondrial damage. Hypoxia reduces the level of pH in cells, which will result in the increased lactate. The process of transferring that exists in plasma membrane depends on the cellular pH. Thus, the level of Ca²⁺ increases in the cytoplasm. The high concentration of Ca²⁺ contributes in two processes of the cell. First, it enhances MPTP complex (mitochondrial permeability transition pore) and leads to the ATP depletion, mitochondria damage, and apoptosis. Additionally, MPTP has a regulatory role in superoxide and peroxynitrous acid productions and DNA degradation. Second, Ca²⁺ contributes in the peroxynitrous acid production of superoxide, indirectly. This figure shows the important role of Peroxynitrous acid in necrotic cell death by several pathways. Peroxynitrous acid can enter the nucleus and leads to the DNA damage and mutations. DNA degradation is, directly and indirectly, responsible for several varieties of cell processes including necrotic cell death, glucose metabolism, and ATP production