Physiological Functions of Mitochondrial Reactive Oxygen Species

Abstract

Mitochondria are the major energy producers within a cell in the form of adenosine triphosphate by oxidative phosphorylation. Normal mitochondrial metabolism inevitably generates reactive oxygen species (ROS), which have been considered to solely cause cellular damage. Increase of oxidative stress has been linked to various pathologies. Thus, mitochondrial ROS (mROS) were basically proposed as byproducts of oxidative metabolism, which undergo normalized by antioxidant enzymes. However, the mROS have extensively been esteemed to function as signalling molecules to regulate a wide variety of physiology. These phenomena are indeed dependent on mitochondrial redox status, which is dynamically altered under different physiological and pathological conditions. The oxidative stress is incurred by which the redox status is inclined to exceeded oxidation or reduction. Here, we attempt to integrate the recent advances in our understanding of the physiological functions of mROS.Keywords: mitochondrial ROS, oxidative stress, oxidative metabolism, redox signaling, mitochondrial physiology Free Radical Medicine and Biology 2 reactive metabolites of O 2 , including superoxide anion (O 2 ·− ) and hydrogen peroxide (H 2 O 2 ), formed by one-and two-electron reductions of O 2 , respectively [7].In the presence of transition metal ions, the more reactive hydroxyl radical (OH · ) is formed. The O 2 ·− is rapidly dismutated to H 2 O 2 by two dismutases including Cu/ Zn-superoxide dismutase (Cu/ZnSOD) in mitochondrial intermembrane space and manganese-dependent superoxide dismutase (MnSOD) in mitochondrial matrix. Unless the dismutation of O 2 ·− is catalyzed into H 2 O 2 , the radical oxidant promotes DNA damage, protein oxidation and lipid peroxidation in many types of cells. H 2 O 2 is also cell damaging molecule to be degraded to water by catalase [8]. Although the O 2 ·− generation by respiratory complexes is a well-established phenomenon, it is still poorly understood in mechanism [9].Mitochondria have been implicated in the regulation of a number of physiological and pathological processes, including proliferation, differentiation, programmed cell death, innate immunity, autophagy, redox signalling, calcium homeostasis, hypoxic stress responses and stem cell reprogramming [10][11][12][13][14][15][16]. The mROS production contributes to mitochondrial damage in a range of pathologies, which is also is closely related to redox signalling in the cell [4,17]. However, accumulating evidences show that mROS are not only deleterious molecules derived from the cellular metabolism but also indispensable participants in diverse cellular signalling and regulations [18][19][20].In this chapter, we briefly summarize recent developments in our understanding of the involvement of mROS as signalling mediators in redox biology, rather than pathological stress, underlying physiological conditions.

Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress

“…Despite taking part in several OS-related pathologies, mtROS are known to have a role in a variety of physiological processes, including proliferation, differentiation, autophagy, immune cell activation, and aging. Under hypoxic conditions, the cell invokes transcriptional and non-transcriptional responses to increase the supply of oxygen while simultaneously reducing oxygen consumption; these adaptations to hypoxia are enhanced by mtROS (Sena and Chandel, 2012;Choi and Kim, 2020). It has been reported that mtROS function as active signaling molecules for diverse cell differentiation, such as stem cell differentiation, myogenic differentiation, and muscle regeneration (Choi and Kim, 2020).…”

“…Under hypoxic conditions, the cell invokes transcriptional and non-transcriptional responses to increase the supply of oxygen while simultaneously reducing oxygen consumption; these adaptations to hypoxia are enhanced by mtROS (Sena and Chandel, 2012;Choi and Kim, 2020). It has been reported that mtROS function as active signaling molecules for diverse cell differentiation, such as stem cell differentiation, myogenic differentiation, and muscle regeneration (Choi and Kim, 2020). In the context of autophagy, mtROS are required to induce autophagy under starvation to promote cell survival or promote controlled autophagic cell death when survival is not possible (Marchi et al, 2012).…”

“…In fact, mitochondrial dysfunction and consequent excessive ROS production lead to cell senescence and death (Ziegler et al, 2015). However, several studies in Drosophila melanogaster and young mice showed that physiologically controlled mtROS might activate adaptive responses that are beneficial to the organism and extend life span (Choi and Kim, 2020).…”

Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm

“…Additional challenges in the understanding of pancreatic beta cell insulin secretion, include changes to the IMM. Mitochondria are the largest intracellular source of reactive oxygen species (ROS) [38][39][40], specifically from the activities of the ETC, as electrons "leak" and react with oxygen, forming superoxide [41,42]. Cellular mechanisms to counter ROS are facilitated by anti-oxidant enzymes such as mitochondrial superoxide dismutase (SOD2) and reduced glutathione (GSH) [43].…”

Biological Adaptations of Tumor Cells to Radiation Therapy

“…Mitochondria generate the chemical energy that cells need to carry out their biochemical functions through oxidative phosphorylation, the most efficient cellular pathway for the generation of ATP ( 120 ). The structure and function of mitochondria are compromised during different types of stress, including RT, so mitochondria respond through different adaptive mechanisms to support RR and maintain organellar and cellular homeostasis ( Figure 2 ).…”