Mitochondria has attracted the attention as a promising pharmacological
target because the impairment of electron transport chain (ETC) function by ROS
overproduction and disturbances in the process of mitochondrial quality control (i.e.
mitochondrial dynamics (mitochondria fusion/fission) and mitophagy) play a prominent
role in the etiology of highly prevalent diseases like diabetes, hypertension,
neurodegeneration, among others. This has led to the development of mitochondriatargeted
antioxidants in order to achieve a better antioxidant effect at the mitochondrial
milieu. However, these molecules had shown some disappointing outcomes, which may
be the result for a need of a better understanding of the actions of these antioxidant
molecules over mitochondria. To achieve this, it must be considered the interplay
between the sources of ROS during disease, the chemical interconversions of ROS and
their differential reactivity with ETC components. Besides, both mitochondrial
dynamics and mitophagy are regulated by the fitness of mitochondrial function and
ROS signaling. Thus, although beneficial under some context, depletion of ROS
generation might be also detrimental by impairing the signaling allowing the
preservation of healthy mitochondrial function through the elimination of damaged
organelles. This review contrasts all these aspects of mitochondrial function with
available data about mitochondrial damage in specific diseases to give an insight into
the importance of ROS chemistry in the rational desing of such molecules, putting
emphasis in the case of MitoQ.
Keywords: Lipid peroxidation, thiol oxidation, iron, respiratory chain, respiratory
complexes, MitoQ, ischemia-reperfusion, Parkinson disease, neurodegeneration
