Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels.

Ryan J Mailloux

doi:10.1155/2018/7857251

Abstract

For over 40 years, mitochondrial reactive oxygen species (ROS) production and balance has been studied in the context of oxidative distress and tissue damage. However, research over the past decade has demonstrated that the mitochondria have a more complicated relationship with ROS. Superoxide (O2•−) and hydrogen peroxide (H2O2) are the proximal ROS formed by the mitochondria, and the latter molecule is used as a secondary messenger to coordinate oxidative metabolism with changes in cell physiology. Like any other secondary messenger, H2O2 levels need to be regulated through its production and degradation and the mitochondria are enriched with the antioxidant defenses required to degrade ROS formed by nutrient oxidation and respiration. Recent work has also demonstrated that these antioxidant systems also carry the capacity to clear H2O2 formed outside of mitochondria. These observations led to the development of the postulate that the mitochondria serve as “ROS stabilizing devices” that buffer cellular H2O2 levels. Here, I provide an updated view on mitochondrial ROS homeostasis and discuss the “ROS stabilizing” function of the mitochondria in mammalian cells. This will be followed by a hypothetical discussion on the potential function of the mitochondria and proton motive force in degrading cellular H2O2 signals emanating from cytosolic enzymes.

Highlights

IntroductionAfter entry into the electron transport chain (ETC), electrons are ferried through the ubiquinone (UQ) pool and complex III to complex IV, reducing molecular oxygen (O2) to water [1]
reactive oxygen species (ROS) genesis by the mammalian mitochondria relies on the same electron transfer pathways that are involved in nutrient oxidation and the biosynthesis of ATP
Mitochondria serve as a critical source and sink for H2O2, a secondary messenger that mediates cellular redox signals

Summary

Introduction

After entry into the electron transport chain (ETC), electrons are ferried through the ubiquinone (UQ) pool and complex III to complex IV, reducing molecular oxygen (O2) to water [1] Electron transfer through this chain is a thermodynamically favorable process and coupled with the pumping of protons by complexes I, III, and IV [2]. Mitochondria are equipped with antioxidant defenses to quench ROS [5]. Clearance of extramitochondrial H2O2 depends on the redox buffering capacity of the matrix which is influenced by the availability of ROS and NADPH. I elaborate on how this H2O2 buffering function of the mitochondria can potentially quench redox signals emanating from cytosolic ROS producers in response to physiological stimuli (Figure 1)

Mitochondrial H2O2 Homeostasis

Mitochondria as a Sink for Cellular Hydrogen Peroxide

Role of the Mitochondria in Degrading Cytosolic H2O2 Signals

Findings

Conclusion