Mitochondrial Oxidative and Nitrosative Stress as a Therapeutic Target in Diseases

Marı́, Montserrat; Colell, Anna

doi:10.3390/antiox10020314

Cited by 11 publications

(11 citation statements)

References 7 publications

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“…However, it also seems that the dosage matters, as only partial but not a complete deletion of cypD extended the life- and healthspan in mice [ 118 ]. For further detail, we refer the reader to comprehensive reviews included into the recent special issue on mitochondrial oxidative and nitrosative stress as a therapeutic target in diseases [ 119 ].…”

Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

et al. 2021

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Neural tissue is one of the main oxygen consumers in the mammalian body, and a plentitude of metabolic as well as signaling processes within the brain is accompanied by the generation of reactive oxygen (ROS) and nitrogen (RNS) species. Besides the important signaling roles, both ROS and RNS can damage/modify the self-derived cellular components thus promoting neuroinflammation and oxidative stress. While previously, the latter processes were thought to progress linearly with age, newer data point to midlife as a critical turning point. Here, we describe (i) the main pathways leading to ROS/RNS generation within the brain, (ii) the main defense systems for their neutralization and (iii) summarize the recent literature about considerable changes in the energy/ROS homeostasis as well as activation state of the brain’s immune system at midlife. Finally, we discuss the role of calorie restriction as a readily available and cost-efficient antiaging and antioxidant lifestyle intervention.

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Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

et al. 2021

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“…There is increasing relevance of mitochondrial dysfunction as a major driver in neurodegenerative diseases, such as MS ( Barcelos et al, 2019 ; Mari and Colell, 2021 ; Tepavcevic, 2021 ). In this context, also OPC differentiation into myelinating oligodendrocytes leading to myelin repair appears to be a metabolically active process ( Kirischuk et al, 1995 ; Schoenfeld et al, 2010 ) the disturbance of which can contribute to myelin dysfunction, lack of repair, and neurodegeneration ( Barcelos et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria undergo two opposing processes in that they separate and merge using fission and fusion processes in response to changes in energy and stress status ( Liu et al, 2020 ). The imbalance of this dynamic equilibrium can result in cell injury and contribute to developmental and neurodegenerative disorders ( Mari and Colell, 2021 ). Also excessive oxidative and nitrosative stress can mediate neuronal injury, in part via mitochondrial fission or fragmentation.…”

Section: Discussionmentioning

confidence: 99%

TLR4 Associated Signaling Disrupters as a New Means to Overcome HERV-W Envelope-Mediated Myelination Deficits

Göttle

Schichel

Reiche

et al. 2021

Front. Cell. Neurosci.

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Myelin repair in the adult central nervous system (CNS) is driven by successful differentiation of resident oligodendroglial precursor cells (OPCs) and thus constitutes a neurodegenerative process capable to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis (MS). The human endogenous retrovirus type W (HERV-W) represents an MS-specific pathogenic entity, and its envelope (ENV) protein was previously identified as a negative regulator of OPC maturation—hence, it is of relevance in the context of diminished myelin repair. We here focused on the activity of the ENV protein and investigated how it can be neutralized for improved remyelination. ENV-mediated activation of toll like receptor 4 (TLR4) increases inducible nitric oxide synthase (iNOS) expression, prompts nitrosative stress, and results in myelin-associated deficits, such as decreased levels of oligodendroglial maturation marker expression and morphological alterations. The intervention of TLR4 surface expression represents a potential means to rescue such ENV-dependent deficits. To this end, the rescue capacity of specific substances, either modulating V-ATPase activity or myeloid differentiation 2 (MD2)-mediated TLR4 glycosylation status, such as compound 20 (C20), L48H437, or folimycin, was analyzed, as these processes were demonstrated to be relevant for TLR4 surface expression. We found that pharmacological treatment can rescue the maturation arrest of oligodendroglial cells and their myelination capacity and can prevent iNOS induction in the presence of the ENV protein. In addition, downregulation of TLR4 surface expression was observed. Furthermore, mitochondrial integrity crucial for oligodendroglial cell differentiation was affected in the presence of ENV and ameliorated upon pharmacological treatment. Our study, therefore, provides novel insights into possible means to overcome myelination deficits associated with HERV-W ENV-mediated myelin deficits.

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“…Nitrosative stress induces the activation of the nod-like receptor protein-3 inflammasome, which can cause pyroptosis through caspase-1- and caspase-11-mediated cytoplasmic protein gasdermin D ( Mari and Colell, 2021 ). When acute and chronic inflammation occurs, the production rate of ONOO – exceeds the ability of the endogenous ONOO – defense system to scavenge it ( Dedon and Tannenbaum, 2004 ; Galloway et al, 2014 ).…”

Section: Mechanisms Of the Cell Death Caused By Nitrosative Stressmentioning

confidence: 99%

Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress

Wang

Yuan

Chen

et al. 2021

Front. Cell Dev. Biol.

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Nitrosative stress, as an important oxygen metabolism disorder, has been shown to be closely associated with cardiovascular diseases, such as myocardial ischemia/reperfusion injury, aortic aneurysm, heart failure, hypertension, and atherosclerosis. Nitrosative stress refers to the joint biochemical reactions of nitric oxide (NO) and superoxide (O2–) when an oxygen metabolism disorder occurs in the body. The peroxynitrite anion (ONOO–) produced during this process can nitrate several biomolecules, such as proteins, lipids, and DNA, to generate 3-nitrotyrosine (3-NT), which further induces cell death. Among these, protein tyrosine nitration and polyunsaturated fatty acid nitration are the most studied types to date. Accordingly, an in-depth study of the relationship between nitrosative stress and cell death has important practical significance for revealing the pathogenesis and strategies for prevention and treatment of various diseases, particularly cardiovascular diseases. Here, we review the latest research progress on the mechanisms of nitrosative stress-mediated cell death, primarily involving several regulated cell death processes, including apoptosis, autophagy, ferroptosis, pyroptosis, NETosis, and parthanatos, highlighting nitrosative stress as a unique mechanism in cardiovascular diseases.

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Mitochondrial Oxidative and Nitrosative Stress as a Therapeutic Target in Diseases

Abstract: Mitochondria are fundamental to life. [...]

Cited by 11 publications

References 7 publications

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

TLR4 Associated Signaling Disrupters as a New Means to Overcome HERV-W Envelope-Mediated Myelination Deficits

Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress

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