Recent Advances in Medicinal Chemistry

Volume: 2

Indexed in: EBSCO.

Recent Advances in Medicinal Chemistry is a book series focused on leading-edge research on developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, ...
[view complete introduction]

US $
30

*(Excluding Mailing and Handling)



Considerations about Oxidative Damage on the Electron Transport Chain and the Quality Control of Mitochondrial Function for the Design of Mitochondria-Targeted Antioxidants

Pp. 156-179 (24)

C. Cortés-Rojo and A.R. Rodríguez-Orozco

Abstract

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,

Affiliation:

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo. 58030 Morelia, Mich. México.