ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice
Abstract Acute kidney injury (AKI), typically caused by ischemia, is a common clinical complication with a poor prognosis. Although proteinuria is an important prognostic indicator of AKI, the underlying causal mechanism remains unclear. In vitro studies suggest that podocytes have high ATP demands...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54222-0 |
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| _version_ | 1849221074504384512 |
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| author | Masahiro Takahashi Shinya Yamamoto Shigenori Yamamoto Akihiro Okubo Yasuaki Nakagawa Koichiro Kuwahara Taiji Matsusaka Shingo Fukuma Masamichi Yamamoto Michiyuki Matsuda Motoko Yanagita |
| author_facet | Masahiro Takahashi Shinya Yamamoto Shigenori Yamamoto Akihiro Okubo Yasuaki Nakagawa Koichiro Kuwahara Taiji Matsusaka Shingo Fukuma Masamichi Yamamoto Michiyuki Matsuda Motoko Yanagita |
| author_sort | Masahiro Takahashi |
| collection | DOAJ |
| description | Abstract Acute kidney injury (AKI), typically caused by ischemia, is a common clinical complication with a poor prognosis. Although proteinuria is an important prognostic indicator of AKI, the underlying causal mechanism remains unclear. In vitro studies suggest that podocytes have high ATP demands to maintain their structure and function, however, analyzing their ATP dynamics in living kidneys has been technically challenging. Here, using intravital imaging to visualize a FRET-based ATP biosensor expressed systemically in female mice due to their suitability for glomerular imaging, we monitor the in vivo ATP dynamics in podocytes during ischemia reperfusion injury. ATP levels decrease during ischemia, but recover after reperfusion in podocytes, exhibiting better recovery than in glomerular endothelial cells. However, prolonged ischemia results in insufficient ATP recovery in podocytes, which is inversely correlated with mitochondrial fragmentation and foot process effacement during the chronic phase. Furthermore, preventing mitochondrial fission via pharmacological inhibition ameliorates podocyte injury in vitro, ex vivo, and in vivo. Thus, these findings provide several insights into how ATP depletion and mitochondrial fragmentation contribute to podocyte injury after ischemic AKI and could potentially be therapeutic targets. |
| format | Article |
| id | doaj-art-5c8ccc38e1e243c4ab45e46a8d770f41 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5c8ccc38e1e243c4ab45e46a8d770f412024-11-24T12:34:03ZengNature PortfolioNature Communications2041-17232024-11-0115111910.1038/s41467-024-54222-0ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female miceMasahiro Takahashi0Shinya Yamamoto1Shigenori Yamamoto2Akihiro Okubo3Yasuaki Nakagawa4Koichiro Kuwahara5Taiji Matsusaka6Shingo Fukuma7Masamichi Yamamoto8Michiyuki Matsuda9Motoko Yanagita10Department of Nephrology, Graduate School of Medicine, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto UniversityDepartment of Cardiovascular Medicine, Shinshu University School of MedicineInstitute of Medical Science and Department of Physiology, Tokai University School of MedicineHuman Health Sciences, Graduate School of Medicine, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityLaboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityAbstract Acute kidney injury (AKI), typically caused by ischemia, is a common clinical complication with a poor prognosis. Although proteinuria is an important prognostic indicator of AKI, the underlying causal mechanism remains unclear. In vitro studies suggest that podocytes have high ATP demands to maintain their structure and function, however, analyzing their ATP dynamics in living kidneys has been technically challenging. Here, using intravital imaging to visualize a FRET-based ATP biosensor expressed systemically in female mice due to their suitability for glomerular imaging, we monitor the in vivo ATP dynamics in podocytes during ischemia reperfusion injury. ATP levels decrease during ischemia, but recover after reperfusion in podocytes, exhibiting better recovery than in glomerular endothelial cells. However, prolonged ischemia results in insufficient ATP recovery in podocytes, which is inversely correlated with mitochondrial fragmentation and foot process effacement during the chronic phase. Furthermore, preventing mitochondrial fission via pharmacological inhibition ameliorates podocyte injury in vitro, ex vivo, and in vivo. Thus, these findings provide several insights into how ATP depletion and mitochondrial fragmentation contribute to podocyte injury after ischemic AKI and could potentially be therapeutic targets.https://doi.org/10.1038/s41467-024-54222-0 |
| spellingShingle | Masahiro Takahashi Shinya Yamamoto Shigenori Yamamoto Akihiro Okubo Yasuaki Nakagawa Koichiro Kuwahara Taiji Matsusaka Shingo Fukuma Masamichi Yamamoto Michiyuki Matsuda Motoko Yanagita ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice Nature Communications |
| title | ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| title_full | ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| title_fullStr | ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| title_full_unstemmed | ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| title_short | ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| title_sort | atp dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice |
| url | https://doi.org/10.1038/s41467-024-54222-0 |
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