Superoxide d splitt1/2/2024 ![]() ![]() These reactions are among the main sources of H 2O 2 in vivo and are either nonenzymatic or catalyzed by superoxide dismutases (SODs). − also produce H 2O 2 as a result of disproportionation reactions ( Gille and Sigler, 1995).This is produced by single-electron reduction of oxygen to a large extent by electron carriers of the respiratory chain in the mitochondria ( Lambert and Brand, 2004). The first intermediate in the sequential reduction of oxygen is often O 2 ), and their formation can result in damage to proteins, lipids, and nucleic acids ( Aung-Htut et al., 2012).−), hydrogen peroxide (H 2O 2), and the hydroxyl radical (OH.ROS commonly formed in vivo include the superoxide radical anion (O 2 The molecules and radicals formed by the incomplete reduction of oxygen are termed reactive oxygen species (ROS Halliwell and Gutteridge, 1989). This toxicity is mainly due to partially reduced forms of O 2 ( Gille and Sigler, 1995), since the O 2 molecule per se has low reactivity ( Halliwell and Gutteridge, 1990). Increased intracellular levels of oxygen, however, are potentially toxic. Most organisms rely on the role of oxygen as a terminal electron acceptor for efficient energy production in the form of ATP. These opposing, concentration-dependent roles of the superoxide radical comprise a form of hormesis and show one ROS having a hormetic effect on the toxicity of another. High levels of the superoxide radical are still toxic. This provides a direct link between complex III as the main source of ROS and its role in defense against ROS. Small increases in levels of mitochondrially produced superoxide radicals have a protective effect during H 2O 2-induced stress, and in response to H 2O 2, the wild-type strain increases superoxide radical production to activate this defense mechanism. Consistent with this correlation, overexpression of superoxide dismutase increases sensitivity to H 2O 2, and this phenotype is partially rescued by addition of small concentrations of menadione. Of interest, the same H 2O 2-sensitive mutant strains have the lowest superoxide radical levels, and strains with the highest resistance to H 2O 2 have the highest levels of superoxide radicals. Disruption of complex III renders cells sensitive to H 2O 2 but not to the superoxide radical generator menadione. Respiratory chain complex III and possibly cytochrome b function are essential for this increase. After H 2O 2 treatment, yeast cells significantly increase superoxide radical production. Our work raises hope that pharmacological manipulation of the mitophagic pathway together with mitochondrially targeted antioxidants may provide new insights leading to promising treatment for these highly lethal conditions.Reactive oxygen species (ROS) consist of potentially toxic, partly reduced oxygen species and free radicals. Our findings provide some additional insights into mitochondrial dysfunction associated with Barth syndrome, but also show that mitophagy inhibition is concomitant with apoptosis dysfunction through the inability of abnormal mitochondrial cardiolipin to assume its role in cytoplasmic signal transduction. Using a HeLa cell model of tafazzin deficiency, we show that dysregulation of tafazzin in HeLa cells induces alteration of mitophagy. Here, we investigated the role of tafazzin in mitochondrial homeostasis dysregulation and mitophagy alteration. All the mitochondrial events are positioned in a context where mitophagy is a key element in mitochondrial quality control. We again highlight the fact that the tafazzin deficiency is also linked to defective oxidative phosphorylation associated with oxidative stress. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. Mutations of the tafazzin gene cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. Abstract : Tafazzin is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation.
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