scholarly journals An Overview of the Ferroptosis Hallmarks in Friedreich’s Ataxia

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1489
Author(s):  
Riccardo Turchi ◽  
Raffaella Faraonio ◽  
Daniele Lettieri-Barbato ◽  
Katia Aquilano
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Protein ◽  
Disease Onset ◽  
Friedreich’S Ataxia ◽  
Therapeutic Strategies ◽  
Friedreich's Ataxia ◽  
Early Mortality ◽  
Molecular Characteristics ◽  
Oxygen Species ◽  
Molecular Alterations

Background: Friedreich’s ataxia (FRDA) is a neurodegenerative disease characterized by early mortality due to hypertrophic cardiomyopathy. FRDA is caused by reduced levels of frataxin (FXN), a mitochondrial protein involved in the synthesis of iron-sulphur clusters, leading to iron accumulation at the mitochondrial level, uncontrolled production of reactive oxygen species and lipid peroxidation. These features are also common to ferroptosis, an iron-mediated type of cell death triggered by accumulation of lipoperoxides with distinct morphological and molecular characteristics with respect to other known cell deaths. Scope of review: Even though ferroptosis has been associated with various neurodegenerative diseases including FRDA, the mechanisms leading to disease onset/progression have not been demonstrated yet. We describe the molecular alterations occurring in FRDA that overlap with those characterizing ferroptosis. Major conclusions: The study of ferroptotic pathways is necessary for the understanding of FRDA pathogenesis, and anti-ferroptotic drugs could be envisaged as therapeutic strategies to cure FRDA.

scholarly journals Decrease in generation of reactive oxygen species by neutrophils from patients with infectious mononucleosis: role of suppressor T lymphocytes

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 994-999
Author(s):  
Y Niwa ◽  
T Sakane ◽  
Y Miyachi ◽  
T Kanoh ◽  
K Somiya
Keyword(s):  
Reactive Oxygen Species ◽  
T Lymphocytes ◽  
Infectious Mononucleosis ◽  
Disease Onset ◽  
Reactive Oxygen ◽  
Control Group ◽  
Ros Generation ◽  
Oxygen Species ◽  
Suppressor T Lymphocytes ◽  
Subsets Of T Lymphocytes

We assessed the generation of reactive oxygen species (ROS: O2-, H2O2, OH . , chemiluminescence) by neutrophils and monocytes from six patients with infectious mononucleosis, ten patients with other viral diseases, and ten normal controls. Neutrophils from infectious mononucleosis patients showed markedly decreased generation of all reactive oxygen species, compared with the two control groups; this abnormality persisted for four to eight weeks after disease onset. Monocytes from these patients generated normal levels of ROS. Normal neutrophils incubated with T lymphocytes from infectious mononucleosis patients generated significantly less of each ROS than did those incubated with T cells from either control group. T cell-mediated suppression of ROS generation required both OKT4+ cells from infectious mononucleosis patients and OKT8+ cells from either patients or normals. We conclude that the generation of reaction oxygen species in neutrophils is suppressed in patients with infectious mononucleosis, at least in part, by interacting subsets of T lymphocytes.

Mitochondrial-derived reactive oxygen species influence ADP sensitivity, but not CPT-I substrate sensitivity

2018 ◽  
Vol 475 (18) ◽  
pp. 2997-3008 ◽  
Author(s):  
Pierre-Andre Barbeau ◽  
Paula M. Miotto ◽  
Graham P. Holloway
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Acute Exercise ◽  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Emission Rates ◽  
Mitochondrial Ros ◽  
Cpt I

The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined; however, key mitochondrial proteins, including carnitine palmitoyltransferase-I (CPT-I) and adenine nucleotide translocase, have redox-sensitive sites. Interestingly, muscle contraction has recently been shown to increase mitochondrial membrane potential and reactive oxygen species (ROS) production; therefore, we aimed to determine if mitochondrial-derived ROS influences bioenergetic responses to exercise. Specifically, we examined the influence of acute exercise on mitochondrial bioenergetics in WT (wild type) and transgenic mice (MCAT, mitochondrial-targeted catalase transgenic) possessing attenuated mitochondrial ROS. We found that ablating mitochondrial ROS did not alter palmitoyl-CoA (P-CoA) respiratory kinetics or influence the exercise-mediated reductions in malonyl CoA sensitivity, suggesting that mitochondrial ROS does not regulate CPT-I. In contrast, while mitochondrial protein content, maximal coupled respiration, and ADP (adenosine diphosphate) sensitivity in resting muscle were unchanged in the absence of mitochondrial ROS, exercise increased the apparent ADP Km (decreased ADP sensitivity) ∼30% only in WT mice. Moreover, while the presence of P-CoA decreased ADP sensitivity, it did not influence the basic response to exercise, as the apparent ADP Km was increased only in the presence of mitochondrial ROS. This basic pattern was also mirrored in the ability of ADP to suppress mitochondrial H2O2 emission rates, as exercise decreased the suppression of H2O2 only in WT mice. Altogether, these data demonstrate that while exercise-induced mitochondrial-derived ROS does not influence CPT-I substrate sensitivity, it inhibits ADP sensitivity independent of P-CoA. These data implicate mitochondrial redox signaling as a regulator of oxidative phosphorylation.

Rheumatoid Arthritis: The Role of Reactive Oxygen Species in Disease Development and Therapeutic Strategies

2007 ◽  
Vol 9 (10) ◽  
pp. 1541-1568 ◽  
Author(s):  
Kyra A. Gelderman ◽  
Malin Hultqvist ◽  
Lina M. Olsson ◽  
Kristin Bauer ◽  
Angela Pizzolla ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Therapeutic Strategies ◽  
Disease Development ◽  
Oxygen Species

scholarly journals Persistent Oxidative Stress Due to Absence of Uncoupling Protein 2 Associated with Impaired Pancreatic β-Cell Function

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3040-3048 ◽  
Author(s):  
Jingbo Pi ◽  
Yushi Bai ◽  
Kiefer W. Daniel ◽  
Dianxin Liu ◽  
Otis Lyght ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Insulin Secretion ◽  
Cell Function ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2−/− mice on three highly congenic (N >10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2−/− mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2−/− mice of mixed 129/B6 strain background, glucose-stimulated insulin secretion in Ucp2−/− islets of each congenic strain was significantly decreased. These data show that the chronic absence of UCP2 causes oxidative stress, including in islets, and is accompanied by impaired glucose-stimulated insulin secretion.

scholarly journals Mutation at position 5628 in the mitochondrial tRNAAla gene in a Chinese pedigree with maternally diabetes mellitus

2019 ◽  
Author(s):  
Ke Li ◽  
Lijun Wu ◽  
Wei Lin ◽  
Tianlan Zhao ◽  
Qiang Qi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Protein Synthesis ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
Molecular Characteristics ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cellular Models ◽  
Mitochondrial Diabetes

Abstract Background: To investigate the clinical, genetic and molecular characteristics of mitochondrial diabetes mellitus (MDM). Methods: Resultant variants were evaluated for evolutionary conservation, allelic frequencies, and structural and functional consequences. The mitochondrial function including mitochondrial tRNAAla levels, protein synthesis, membrane potential, adenosine triphosphate (ATP) production, and reactive oxygen species (ROS) generation were measured using lymphoblastoid cell lines carrying the m.5628T>C mutation and 2 controls .Results: We observed differences in the severity and age of onset in diabetes in affected maternally-related individuals, and through amolecular of the complete mitochondrial genome in this family, we identified a homoplasmic m.5628T>C mutation, located at conventional position 31 of tRNAAla, and we further detected distinct sets of mtDNA polymorphisms belonging to haplogroup L1. The identified mutation was further found be important for tRNA identity and stability. Using cellular models, we were able to determine that the respiratory deficiency caused arising as a consequence of the m.5628T>C mutation led to decreased efficiency of mitochondrial tRNAAla levels, protein synthesis, mitochondrial ATP synthesis and a reduced mitochondrial membrane potential.These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cell lines. Conclusions: These data provide a direct evidence that novel m.5628T>C mutation may be associated with MDM, thus, offering novel insights into the understanding of pathophysiology of MDM.

scholarly journals Ferroptosis in Friedreich’s Ataxia: A Metal-Induced Neurodegenerative Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1551
Author(s):  
Piergiorgio La Rosa ◽  
Sara Petrillo ◽  
Maria Teresa Fiorenza ◽  
Enrico Silvio Bertini ◽  
Fiorella Piemonte
Keyword(s):  
Cell Death ◽  
Neurodegenerative Disease ◽  
Neuronal Cell Death ◽  
Mitochondrial Protein ◽  
Neuronal Cell ◽  
Antioxidant Response ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Antioxidant Defenses ◽  
Special Focus

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich’s Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress.

scholarly journals Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-Yu Chen ◽  
Huan-Huan Ren ◽  
Dan Wang ◽  
Ying Chen ◽  
Chuan-Jun Qu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Protein ◽  
Reactive Oxygen ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Mitochondrial Target ◽  
Sulfur Protein ◽  
A375 Cells

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.

scholarly journals Antioxidants: Positive or Negative Actors?

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 124 ◽  
Author(s):  
Bahare Salehi ◽  
Miquel Martorell ◽  
Jack Arbiser ◽  
Antoni Sureda ◽  
Natália Martins ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Current Knowledge ◽  
Disease Onset ◽  
Reactive Oxygen ◽  
Population Based ◽  
Reactive Species ◽  
Oxygen Species ◽  
A Cell ◽  
Nuanced Understanding ◽  
Definition Of

The term “antioxidant” is one of the most confusing definitions in biological/medical sciences. In chemistry, “antioxidant” is simply conceived “a compound that removes reactive species, mainly those oxygen-derived”, while in a cell context, the conceptual definition of an antioxidant is poorly understood. Indeed, non-clinically recommended antioxidants are often consumed in large amounts by the global population, based on the belief that cancer, inflammation and degenerative diseases are triggered by high oxygen levels (or reactive oxygen species) and that through blocking reactive species production, organic unbalances/disorders can be prevented and/or even treated. The popularity of these chemicals arises in part from the widespread public mistrust of allopathic medicine. In fact, reactive oxygen species play a dual role in dealing with different disorders, since they may contribute to disease onset and/or progression but may also play a key role in disease prevention. Further, the ability of the most commonly used supplements, such as vitamins C, E, selenium, and herbal supplements to decrease pathologic reactive oxygen species is not clearly established. Hence, the present review aims to provide a nuanced understanding of where current knowledge is and where it should go.

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