Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances

Abstract Mitochondria are the energy production centers in cells and have unique genetic information. Due to the irreplaceable function of mitochondria, mitochondrial dysfunction often leads to pathological changes. Mitochondrial dysfunction induces an imbalance between oxidation and antioxidation,...

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Main Authors: Xieyang Xu, Yan Pang, Xianqun Fan
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-025-02253-4
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author Xieyang Xu
Yan Pang
Xianqun Fan
author_facet Xieyang Xu
Yan Pang
Xianqun Fan
author_sort Xieyang Xu
collection DOAJ
description Abstract Mitochondria are the energy production centers in cells and have unique genetic information. Due to the irreplaceable function of mitochondria, mitochondrial dysfunction often leads to pathological changes. Mitochondrial dysfunction induces an imbalance between oxidation and antioxidation, mitochondrial DNA (mtDNA) damage, mitochondrial dynamics dysregulation, and changes in mitophagy. It results in oxidative stress due to excessive reactive oxygen species (ROS) generation, which contributes to cell damage and death. Mitochondrial dysfunction can also trigger inflammation through the activation of damage-associated molecular patterns (DAMPs), inflammasomes and inflammatory cells. Besides, mitochondrial alterations in the functional regulation, energy metabolism and genetic stability accompany the aging process, and there has been a lot of evidence suggesting that oxidative stress and inflammation, both of which are associated with mitochondrial dysfunction, are predisposing factors of aging. Therefore, this review hypothesizes that mitochondria serve as central hubs regulating oxidative stress, inflammation, and aging, and their dysfunction contributes to various diseases, including cancers, cardiovascular diseases, neurodegenerative disorders, metabolic diseases, sepsis, ocular pathologies, liver diseases, and autoimmune conditions. Moreover, we outline therapies aimed at various mitochondrial dysfunctions, highlighting their performance in animal models and human trials. Additionally, we focus on the limitations of mitochondrial therapy in clinical applications, and discuss potential future research directions for mitochondrial therapy.
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spelling doaj-art-53a6ea8b47e644c8bf1d10e1ee58d6a22025-08-20T03:21:06ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-06-0110112910.1038/s41392-025-02253-4Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advancesXieyang Xu0Yan Pang1Xianqun Fan2Department of Ophthalmology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Ophthalmology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Mitochondria are the energy production centers in cells and have unique genetic information. Due to the irreplaceable function of mitochondria, mitochondrial dysfunction often leads to pathological changes. Mitochondrial dysfunction induces an imbalance between oxidation and antioxidation, mitochondrial DNA (mtDNA) damage, mitochondrial dynamics dysregulation, and changes in mitophagy. It results in oxidative stress due to excessive reactive oxygen species (ROS) generation, which contributes to cell damage and death. Mitochondrial dysfunction can also trigger inflammation through the activation of damage-associated molecular patterns (DAMPs), inflammasomes and inflammatory cells. Besides, mitochondrial alterations in the functional regulation, energy metabolism and genetic stability accompany the aging process, and there has been a lot of evidence suggesting that oxidative stress and inflammation, both of which are associated with mitochondrial dysfunction, are predisposing factors of aging. Therefore, this review hypothesizes that mitochondria serve as central hubs regulating oxidative stress, inflammation, and aging, and their dysfunction contributes to various diseases, including cancers, cardiovascular diseases, neurodegenerative disorders, metabolic diseases, sepsis, ocular pathologies, liver diseases, and autoimmune conditions. Moreover, we outline therapies aimed at various mitochondrial dysfunctions, highlighting their performance in animal models and human trials. Additionally, we focus on the limitations of mitochondrial therapy in clinical applications, and discuss potential future research directions for mitochondrial therapy.https://doi.org/10.1038/s41392-025-02253-4
spellingShingle Xieyang Xu
Yan Pang
Xianqun Fan
Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
Signal Transduction and Targeted Therapy
title Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
title_full Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
title_fullStr Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
title_full_unstemmed Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
title_short Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
title_sort mitochondria in oxidative stress inflammation and aging from mechanisms to therapeutic advances
url https://doi.org/10.1038/s41392-025-02253-4
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AT yanpang mitochondriainoxidativestressinflammationandagingfrommechanismstotherapeuticadvances
AT xianqunfan mitochondriainoxidativestressinflammationandagingfrommechanismstotherapeuticadvances