Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport

Onukwufor, John O.; Berry, Brandon J.; Wojtovich, Andrew P.

doi:10.3390/antiox8080285

Cited by 73 publications

(52 citation statements)

References 100 publications

(194 reference statements)

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“…In the mitochondrial transport chain, flavoprotein reductase forms ROS by direct reduction of O 2 and via the mediation of quinones. [ 104 ]. Superoxide (O 2 −• ) is produced by XO in the reperfusion phase of ischemia, LOX, COX, and NADPH-dependent oxidase [ 105 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

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Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

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Section: Oxidative Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

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“…Reverse electron transfer (RET) catalyzed superoxide production was discovered by Chance and co-workers in 1967 [ 71 ], and was considered irrelevant, until Murphy’s group showed that RET contributed to cardiac ischemia reperfusion injury (IRI) in 2013–2014 [ 72 , 73 ]. We now know that RET plays several important physiological (e.g., sleep, lifespan and O 2 sensing) and pathological (e.g., in organ transplantation) roles [ 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. Robb and colleagues [ 81 ] have identified the factors that govern RET: a highly reduced Q pool and near maximal Δ p .…”

Section: Mechanisms Of Mitochondrial Ros Production: the Knownmentioning

confidence: 99%

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Cobley

2020

Antioxidants

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The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte/zygote mitochondria—a major presumptive oxidative stressor—produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.

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“…In addition, oxidized lipids and mitochondrial redox state were assayed, and mito-dR decreased signs of oxidative stress. In many contexts, however, decreased rather than increased PMF is associated with alleviated oxidative stress [6, 79,80], especially in Parkinson's disease models [81][82][83][84].…”

Section: Mito-drmentioning

confidence: 99%

Mitochondrial light switches: optogenetic approaches to control metabolism

Berry

Wojtovich

2020

The FEBS Journal

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Developing new technologies to study metabolism is increasingly important as metabolic disease prevalence increases. Mitochondria control cellular metabolism and dynamic changes in mitochondrial function are associated with metabolic abnormalities in cardiovascular disease, cancer, and obesity. However, a lack of precise and reversible methods to control mitochondrial function has prevented moving from association to causation. Recent advances in optogenetics have addressed this challenge, and mitochondrial function can now be precisely controlled in vivo using light. A class of genetically encoded, light-activated membrane channels and pumps has addressed mechanistic questions that promise to provide new insights into how cellular metabolism downstream of mitochondrial function contributes to disease. Here, we highlight emerging reagents-mitochondria-targeted light-activated cation channels or proton pumps-to decrease or increase mitochondrial activity upon light exposure, a technique we refer to as mitochondrial light switches, or mt SWITCH. The mt SWITCH technique is broadly applicable, as energy availability and metabolic signaling are conserved aspects of cellular function and health. Here, we outline the use of these tools in diverse cellular models of disease. We review the molecular details of each optogenetic tool, summarize the results obtained with each, and outline best practices for using optogenetic approaches to control mitochondrial function and downstream metabolism.

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Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport

Cited by 73 publications

References 100 publications

Monitoring the Redox Status in Multiple Sclerosis

Monitoring the Redox Status in Multiple Sclerosis

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Mitochondrial light switches: optogenetic approaches to control metabolism

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