The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence
The regulation of mitochondria function and health is a central node in tissue maintenance, ageing as well as the pathogenesis of various diseases. However, the maintenance of an active mitochondrial functional state and its quality control mechanisms remain incompletely understood. By studying mice...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722002191 |
| _version_ | 1818021007284240384 |
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| author | Yinyin Xie Yannan Zhang Aina Sun Yamei Peng Weikang Hou Cong Xiang Guoxin Zhang Beibei Lai Xiaoshuang Hou Fangfang Zheng Fan Wang Geng Liu |
| author_facet | Yinyin Xie Yannan Zhang Aina Sun Yamei Peng Weikang Hou Cong Xiang Guoxin Zhang Beibei Lai Xiaoshuang Hou Fangfang Zheng Fan Wang Geng Liu |
| author_sort | Yinyin Xie |
| collection | DOAJ |
| description | The regulation of mitochondria function and health is a central node in tissue maintenance, ageing as well as the pathogenesis of various diseases. However, the maintenance of an active mitochondrial functional state and its quality control mechanisms remain incompletely understood. By studying mice with a mitochondria-targeted reporter that shifts its fluorescence from “green” to “red” with time (MitoTimer), we found MitoTimer fluorescence spectrum was heavily dependent on the oxidative metabolic state in the skeletal muscle fibers. The mitoproteolytic activity was enhanced in an energy dependent manner, and accelerated the turnover of MitoTimer protein and respiratory chain substrate, responsible for a green predominant MitoTimer fluorescence spectrum under the oxidative conditions. PGC1α, as well as anti-ageing regents promoted enhanced mitoproteolysis. In addition, cells with the green predominant mitochondria exhibited lower levels of MitoSox and protein carbonylation, indicating a favorable redox state. Thus, we identified MitoTimer as a probe for mitoproteolytic activity in vivo and found a heightened control of mitoproteolysis in the oxidative metabolic state, providing a framework for understanding the maintenance of active oxidative metabolism while limiting oxidative damages. |
| first_indexed | 2024-04-14T08:13:13Z |
| format | Article |
| id | doaj.art-c9f5e382db92494a801e247f6c91b1bf |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-14T08:13:13Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-c9f5e382db92494a801e247f6c91b1bf2022-12-22T02:04:29ZengElsevierRedox Biology2213-23172022-10-0156102447The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescenceYinyin Xie0Yannan Zhang1Aina Sun2Yamei Peng3Weikang Hou4Cong Xiang5Guoxin Zhang6Beibei Lai7Xiaoshuang Hou8Fangfang Zheng9Fan Wang10Geng Liu11State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaCorresponding author.; State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study and Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, School of Medicine, Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province, 210061, ChinaThe regulation of mitochondria function and health is a central node in tissue maintenance, ageing as well as the pathogenesis of various diseases. However, the maintenance of an active mitochondrial functional state and its quality control mechanisms remain incompletely understood. By studying mice with a mitochondria-targeted reporter that shifts its fluorescence from “green” to “red” with time (MitoTimer), we found MitoTimer fluorescence spectrum was heavily dependent on the oxidative metabolic state in the skeletal muscle fibers. The mitoproteolytic activity was enhanced in an energy dependent manner, and accelerated the turnover of MitoTimer protein and respiratory chain substrate, responsible for a green predominant MitoTimer fluorescence spectrum under the oxidative conditions. PGC1α, as well as anti-ageing regents promoted enhanced mitoproteolysis. In addition, cells with the green predominant mitochondria exhibited lower levels of MitoSox and protein carbonylation, indicating a favorable redox state. Thus, we identified MitoTimer as a probe for mitoproteolytic activity in vivo and found a heightened control of mitoproteolysis in the oxidative metabolic state, providing a framework for understanding the maintenance of active oxidative metabolism while limiting oxidative damages.http://www.sciencedirect.com/science/article/pii/S2213231722002191MitoproteolysisMitoTimerOxidative metabolismPGC-1αMuscle fiber type |
| spellingShingle | Yinyin Xie Yannan Zhang Aina Sun Yamei Peng Weikang Hou Cong Xiang Guoxin Zhang Beibei Lai Xiaoshuang Hou Fangfang Zheng Fan Wang Geng Liu The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence Redox Biology Mitoproteolysis MitoTimer Oxidative metabolism PGC-1α Muscle fiber type |
| title | The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence |
| title_full | The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence |
| title_fullStr | The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence |
| title_full_unstemmed | The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence |
| title_short | The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimer fluorescence |
| title_sort | coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through mitotimer fluorescence |
| topic | Mitoproteolysis MitoTimer Oxidative metabolism PGC-1α Muscle fiber type |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722002191 |
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