Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus
Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial react...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.929520/full |
| _version_ | 1811312817226121216 |
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| author | Like Zhao Xianda Hu Fei Xiao Fei Xiao Xuan Zhang Lidan Zhao Lidan Zhao Min Wang |
| author_facet | Like Zhao Xianda Hu Fei Xiao Fei Xiao Xuan Zhang Lidan Zhao Lidan Zhao Min Wang |
| author_sort | Like Zhao |
| collection | DOAJ |
| description | Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE. |
| first_indexed | 2024-04-13T10:43:18Z |
| format | Article |
| id | doaj.art-26f2b01912074bc5a5239f6fc5e755fa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T10:43:18Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-26f2b01912074bc5a5239f6fc5e755fa2022-12-22T02:49:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.929520929520Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosusLike Zhao0Xianda Hu1Fei Xiao2Fei Xiao3Xuan Zhang4Lidan Zhao5Lidan Zhao6Min Wang7Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Tibetan Hospital, China Tibetology Research Center, Beijing, ChinaThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaClinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNational Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology, Beijing, ChinaDepartment of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaNucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE.https://www.frontiersin.org/articles/10.3389/fimmu.2022.929520/fullsystemic lupus erythematosusmitochondrial reactive oxygen speciesmitochondrial dysfunctionmitophagyoxidative stressmitochondria targeting therapeutics |
| spellingShingle | Like Zhao Xianda Hu Fei Xiao Fei Xiao Xuan Zhang Lidan Zhao Lidan Zhao Min Wang Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus Frontiers in Immunology systemic lupus erythematosus mitochondrial reactive oxygen species mitochondrial dysfunction mitophagy oxidative stress mitochondria targeting therapeutics |
| title | Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| title_full | Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| title_fullStr | Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| title_full_unstemmed | Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| title_short | Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| title_sort | mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus |
| topic | systemic lupus erythematosus mitochondrial reactive oxygen species mitochondrial dysfunction mitophagy oxidative stress mitochondria targeting therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.929520/full |
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