The roles and mechanisms of CDGSH iron-sulfur domain 1 in kainic acid-induced mitochondrial iron overload, dysfunction and neuronal damage - 17/05/25
Abstract |
Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe2 + remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using in vivo and in vitro excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
CISD1 resists neuronal damage caused by KA by promoting mitochondrial iron output and inhibiting mitochondrial dysfunction. KA mediates downregulation of SIRT1, increases acetylation level of CISD1 and downregulates CISD1 expression, resulting in decreased mitochondrial iron output capacity and mitochondrial iron overload; SIRT1-specific agonist SRT1460 can restore the function of deacetylase SIRT1, upregulate CISD1 expression, and inhibit neuronal death; DFO or upregulation of CISD1 can inhibit mitochondrial iron overload, improve mitochondrial respiratory function, and effectively protect neurons from damage caused by KA. SIRT1, Sirtuin 1; CISD1, CDGSH Iron-Sulfur Domain 1. The image was drawn using BioRender.com.
CISD1 resists neuronal damage caused by KA by promoting mitochondrial iron output and inhibiting mitochondrial dysfunction. KA mediates downregulation of SIRT1, increases acetylation level of CISD1 and downregulates CISD1 expression, resulting in decreased mitochondrial iron output capacity and mitochondrial iron overload; SIRT1-specific agonist SRT1460 can restore the function of deacetylase SIRT1, upregulate CISD1 expression, and inhibit neuronal death; DFO or upregulation of CISD1 can inhibit mitochondrial iron overload, improve mitochondrial respiratory function, and effectively protect neurons from damage caused by KA. SIRT1, Sirtuin 1; CISD1, CDGSH Iron-Sulfur Domain 1. The image was drawn using BioRender.com.Le texte complet de cet article est disponible en PDF.
Highlights |
• | CISD1 protects neurons from KA damage by enhancing iron output and preventing mitochondrial dysfunction. |
• | CISD1 acetylation increases under KA excitotoxicity. |
• | SIRT1 agonist SRT1460 upregulates the level of CISD1. |
Keywords : CISD1, SIRT1, Neuronal excitotoxicity, Mitochondrial dysfunction, Iron overload
Plan
Vol 187
Article 118067- juin 2025 Retour au numéro
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