Excessive Production of Hydrogen Peroxide in Mitochondria Contributes to Atopic Dermatitis

Minzaghi, Deborah; Pavel, Petra; Kremslehner, Christopher; Грубер, Флориан; Oberreiter, Sophie; Hagenbuchner, Judith; Frari, Barbara Del; Blunder, Stefan; Gruber, Robert; Dubrac, Sandrine

doi:10.1016/j.jid.2023.03.1680

Cited by 10 publications

(8 citation statements)

References 82 publications

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“…Previous targeted microarray-based studies have demonstrated de-coordinated anti-oxidative response in AD epidermis ( 14 ). The fact that some down-regulated antioxidant genes support mitochondrial quality control in multiple ways is noteworthy.…”

Section: Discussionmentioning

confidence: 99%

“…It is proposed that mitochondria play an important role in the pathogenesis of AD. Abnormal levels of mitochondrial metabolism and mitochondrial respiration in pro-oxidative situations have been gradually identified as a potential distinguishing characteristic of inflammatory illnesses like AD ( 5 , 14 , 15 ). Topical application of MitoQ, a mitochondrial targeting antioxidant, has been shown to effectively ameliorate AD-like eczema in mice through anti-inflammatory and antioxidant effects ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…Abnormal levels of mitochondrial metabolism and mitochondrial respiration in pro-oxidative situations have been gradually identified as a potential distinguishing characteristic of inflammatory illnesses like AD ( 5 , 14 , 15 ). Topical application of MitoQ, a mitochondrial targeting antioxidant, has been shown to effectively ameliorate AD-like eczema in mice through anti-inflammatory and antioxidant effects ( 14 ). It is necessary to uncover novel critical mitochondria-related genes, in light of aberrant mitochondria activity in the course of AD, to better understand the potential mechanism of AD and provide new ideas for molecular diagnosis and therapy for these patients.…”

Section: Introductionmentioning

confidence: 99%

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Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning

Yu,

Lin,

Yuan

et al. 2024

Front. Immunol.

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BackgroundThere is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD.MethodsPublic data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients.ResultsMitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells’ infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms.ConclusionsThe study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning

Yu,

Lin,

Yuan

et al. 2024

Front. Immunol.

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“…Another study found that an excessive production of hydrogen peroxide in mitochondria contributes to atopic dermatitis [ 66 ]. The study found increased levels of SOD2 and hydrogen peroxide in the mitochondria of flaky tail mouse keratinocytes.…”

Section: Mitochondria Dysfunction and Dermatological Manifestationsmentioning

confidence: 99%

“…After topical application of MitoQ to flaky tail mice skin, there was a reduction in inflammation and restoration of epidermal homeostasis. These findings suggest that there is an increase in SOD2 and cytochrome c in the epidermis of AD patients and a reduction in the antioxidant response as a result of mitochondrial dysfunction [ 66 ].…”

Section: Mitochondria Dysfunction and Dermatological Manifestationsmentioning

confidence: 99%

Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature

Natarelli,

Gahoonia,

Aflatooni

et al. 2024

IJMS

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Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

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Exploring novel drug targets for atopic dermatitis through plasma proteome with genome

Wu,

Su,

Chen

et al. 2024

Arch Dermatol Res

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Excessive Production of Hydrogen Peroxide in Mitochondria Contributes to Atopic Dermatitis

Cited by 10 publications

References 82 publications

Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning

Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning

Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature

Exploring novel drug targets for atopic dermatitis through plasma proteome with genome

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