NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport
NDP52, a constituent of the selective autophagy receptors (SARs), was recognized for its involvement in facilitating substrate degradation via autophagic bridging. However, its autonomous function apart from autophagy remained largely unexplored. Here, we reported that NDP52 was down-regulated in de...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725002605 |
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| author | Yutao Zhu Yaohan Xu Dinqi Xie Nengfeng Yu Jiaxin Chen Jiechao Xia Zixuan Mei Yang Jin Chuan Hu Pan Tang Sicheng Jiang Chao Jiang Honghai Song Zhijun Hu |
| author_facet | Yutao Zhu Yaohan Xu Dinqi Xie Nengfeng Yu Jiaxin Chen Jiechao Xia Zixuan Mei Yang Jin Chuan Hu Pan Tang Sicheng Jiang Chao Jiang Honghai Song Zhijun Hu |
| author_sort | Yutao Zhu |
| collection | DOAJ |
| description | NDP52, a constituent of the selective autophagy receptors (SARs), was recognized for its involvement in facilitating substrate degradation via autophagic bridging. However, its autonomous function apart from autophagy remained largely unexplored. Here, we reported that NDP52 was down-regulated in degenerated chondrocytes. Besides, NDP52 deficiency promoted the extracellular matrix (ECM) degradation, inflammation, cell apoptosis and senescence via its autophagy-independent functions. The absence of NDP52 disrupted the flow of electron respiration chains and led to the production of intracellular mitochondrial reactive oxygen species (mtROS). Subsequent mechanistic investigations revealed that the downregulation of NDP52 upregulated the expression levels of mitochondrial complex Ⅰ by modulating MTIF3 expression, leading to reverse electron transport (RET) and mtROS production. Our research highlights the significance of NDP52 in facilitating chondrocyte degeneration and osteoarthritis, and provides insights into the distinctive mechanism by which autophagy receptors NDP52 induce intracellular mitochondrial ROS dysregulation via non-canonical pathways. |
| format | Article |
| id | doaj-art-4b6f59415e634af3aeb854c7decdb9ab |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-4b6f59415e634af3aeb854c7decdb9ab2025-08-24T05:12:27ZengElsevierRedox Biology2213-23172025-09-018510374710.1016/j.redox.2025.103747NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transportYutao Zhu0Yaohan Xu1Dinqi Xie2Nengfeng Yu3Jiaxin Chen4Jiechao Xia5Zixuan Mei6Yang Jin7Chuan Hu8Pan Tang9Sicheng Jiang10Chao Jiang11Honghai Song12Zhijun Hu13Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Urology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, PR ChinaCenter for Plastic & Reconstructive Surgery, Department of Plastic & Reconstructive Surgery, Zhejiang Provincial People's Hospital(Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR China; Department of Orthopaedics, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR China; Corresponding author. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, East Qing Chun Road, Hangzhou, PR China.Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR China; Corresponding author. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, East Qing Chun Road, Hangzhou, PR China.Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, Hangzhou, PR China; Corresponding author. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Key Laboratory of Musculoskeletal System Degeneration, Regeneration Translational Research of Zhejiang Province, East Qing Chun Road, Hangzhou, PR China.NDP52, a constituent of the selective autophagy receptors (SARs), was recognized for its involvement in facilitating substrate degradation via autophagic bridging. However, its autonomous function apart from autophagy remained largely unexplored. Here, we reported that NDP52 was down-regulated in degenerated chondrocytes. Besides, NDP52 deficiency promoted the extracellular matrix (ECM) degradation, inflammation, cell apoptosis and senescence via its autophagy-independent functions. The absence of NDP52 disrupted the flow of electron respiration chains and led to the production of intracellular mitochondrial reactive oxygen species (mtROS). Subsequent mechanistic investigations revealed that the downregulation of NDP52 upregulated the expression levels of mitochondrial complex Ⅰ by modulating MTIF3 expression, leading to reverse electron transport (RET) and mtROS production. Our research highlights the significance of NDP52 in facilitating chondrocyte degeneration and osteoarthritis, and provides insights into the distinctive mechanism by which autophagy receptors NDP52 induce intracellular mitochondrial ROS dysregulation via non-canonical pathways.http://www.sciencedirect.com/science/article/pii/S2213231725002605OsteoarthritisChondrocyteNDP52Mitochondria reactive oxygen species (mtROS)Reverse electron transport (RET)MTIF3 |
| spellingShingle | Yutao Zhu Yaohan Xu Dinqi Xie Nengfeng Yu Jiaxin Chen Jiechao Xia Zixuan Mei Yang Jin Chuan Hu Pan Tang Sicheng Jiang Chao Jiang Honghai Song Zhijun Hu NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport Redox Biology Osteoarthritis Chondrocyte NDP52 Mitochondria reactive oxygen species (mtROS) Reverse electron transport (RET) MTIF3 |
| title | NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport |
| title_full | NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport |
| title_fullStr | NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport |
| title_full_unstemmed | NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport |
| title_short | NDP52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ROS via reverse electron transport |
| title_sort | ndp52 deficiency accelerates chondrocyte degeneration through promoting pathogenic mitochondrial ros via reverse electron transport |
| topic | Osteoarthritis Chondrocyte NDP52 Mitochondria reactive oxygen species (mtROS) Reverse electron transport (RET) MTIF3 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725002605 |
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