Oxidative stress and cellular respiration

During cellular respiration, electrons are transferred from NADH or FADH2, along 4 protein complexes in the inner mitochondrial membrane, to an O₂ molecule (read more about this subject here). In the last stage of the process, the electrons are transported one by one, that is, they will reach the oxygen one at a time. 

This situation, which may seem only a detail to many, has, in fact, very important implications for our biochemistry, because it means that all O₂ molecules are, even temporarily, transformed into a free radical, the superoxide anion. This means that, literally, at every instant we are producing large quantities of reactive oxygen species. However, this situation, which is potentially very dangerous, does not have, under normal conditions, dramatic consequences for cells, mainly for 2 reasons:
1. There are mechanisms that prevent the superoxide anion from diffusing from complex 4 before it is completely reduced to water. That is, the free radical is formed, but remains in place and quickly receives another electron, ceasing to be free radical.
2. As there are always some superoxide anions that can escape the first mechanism, we have other defense mechanisms, and in this context, the most important is the presence of a mitochondrial enzyme called superoxide dismutase. This enzyme, which also has a cytosolic isoform, will cause dismutation of the superoxide anion, converting two of these molecules into hydrogen peroxide.
Of course there will also be superoxide anions that will be able to escape from superoxide dismutase, but under normal conditions these are very few. In addition, we still have several other antioxidant defenses waiting for them...

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