ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells
Mitochondrial injury of tubular epithelial cells (TECs) is the key pathogenic event underlying various kidney diseases and a potential intervening target as well. Our previous study demonstrated that ING2 is ubiquitously expressed at tubulointerstitial area within kidneys, while its role in regulati...
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Frontiers Media S.A.
2021-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.700195/full |
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| author | Ying Yang Ying Yang Chensheng Li Xia Gu Junhui Zhen Suwei Zhu Tingting Lv Qiang Wan Yi Liu Yi Liu Yi Liu |
| author_facet | Ying Yang Ying Yang Chensheng Li Xia Gu Junhui Zhen Suwei Zhu Tingting Lv Qiang Wan Yi Liu Yi Liu Yi Liu |
| author_sort | Ying Yang |
| collection | DOAJ |
| description | Mitochondrial injury of tubular epithelial cells (TECs) is the key pathogenic event underlying various kidney diseases and a potential intervening target as well. Our previous study demonstrated that ING2 is ubiquitously expressed at tubulointerstitial area within kidneys, while its role in regulating TEC mitochondrial respiration is not fully elucidated. To clarify the roles of ING2 in mitochondrial homeostasis of TECs and pathogenesis of acute ischemic kidney injury, Western blot, PCR, immunofluorescence, immunoprecipitation, and oxygen consumption rate assay were applied to address the roles of ING2 in modulating mitochondrial respiration. We further complemented these studies with acute ischemic kidney injury both in vitro and in vivo. In vitro study demonstrated ING2 could positively control TEC mitochondrial respiration. Concurrently, both mRNA and protein levels of mtDNA encoded respiratory chain components were altered by ING2, suggesting ING2 could regulate mtDNA transcription. In mechanism, ING2 could regulate the ubiquitination of a newly identified mitochondrial transcription factor MRPL12, thereby modulating its cellular stability and abundance. We also demonstrated ING2-mediated modulation on mtDNA transcription and mitochondrial respiration are involved in serum deprivation induced TEC injuries. Finally, immunohistochemistry study revealed that ING2 expression was significantly altered in kidney biopsies with acute ischemic kidney injury. In vivo study suggested that kidney specific ING2 overexpression could effectively ameliorate acute ischemic kidney injury. Our study demonstrated that ING2 is a crucial modulator of TEC mitochondrial respiration. These findings suggested a unrecognized role of ING2 in TEC mitochondrial energetic homeostasis and a potential intervening target for TEC mitochondrial injury associated pathologies. |
| first_indexed | 2024-12-13T19:38:05Z |
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| id | doaj.art-16593aaf5d5a4037820ec8448f0d486a |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T19:38:05Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-16593aaf5d5a4037820ec8448f0d486a2022-12-21T23:33:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.700195700195ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial CellsYing Yang0Ying Yang1Chensheng Li2Xia Gu3Junhui Zhen4Suwei Zhu5Tingting Lv6Qiang Wan7Yi Liu8Yi Liu9Yi Liu10Department of Pharmacy, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Pathology, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSchool of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, ChinaCentral Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaShandong Key Laboratory of Infectious Respiratory Disease, Jinan, ChinaMitochondrial injury of tubular epithelial cells (TECs) is the key pathogenic event underlying various kidney diseases and a potential intervening target as well. Our previous study demonstrated that ING2 is ubiquitously expressed at tubulointerstitial area within kidneys, while its role in regulating TEC mitochondrial respiration is not fully elucidated. To clarify the roles of ING2 in mitochondrial homeostasis of TECs and pathogenesis of acute ischemic kidney injury, Western blot, PCR, immunofluorescence, immunoprecipitation, and oxygen consumption rate assay were applied to address the roles of ING2 in modulating mitochondrial respiration. We further complemented these studies with acute ischemic kidney injury both in vitro and in vivo. In vitro study demonstrated ING2 could positively control TEC mitochondrial respiration. Concurrently, both mRNA and protein levels of mtDNA encoded respiratory chain components were altered by ING2, suggesting ING2 could regulate mtDNA transcription. In mechanism, ING2 could regulate the ubiquitination of a newly identified mitochondrial transcription factor MRPL12, thereby modulating its cellular stability and abundance. We also demonstrated ING2-mediated modulation on mtDNA transcription and mitochondrial respiration are involved in serum deprivation induced TEC injuries. Finally, immunohistochemistry study revealed that ING2 expression was significantly altered in kidney biopsies with acute ischemic kidney injury. In vivo study suggested that kidney specific ING2 overexpression could effectively ameliorate acute ischemic kidney injury. Our study demonstrated that ING2 is a crucial modulator of TEC mitochondrial respiration. These findings suggested a unrecognized role of ING2 in TEC mitochondrial energetic homeostasis and a potential intervening target for TEC mitochondrial injury associated pathologies.https://www.frontiersin.org/articles/10.3389/fcell.2021.700195/fullING2MRPL12mitochondrial respirationubiquitinationtubular epithelial cellskidney disease |
| spellingShingle | Ying Yang Ying Yang Chensheng Li Xia Gu Junhui Zhen Suwei Zhu Tingting Lv Qiang Wan Yi Liu Yi Liu Yi Liu ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells Frontiers in Cell and Developmental Biology ING2 MRPL12 mitochondrial respiration ubiquitination tubular epithelial cells kidney disease |
| title | ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
| title_full | ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
| title_fullStr | ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
| title_full_unstemmed | ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
| title_short | ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
| title_sort | ing2 controls mitochondrial respiration via modulating mrpl12 ubiquitination in renal tubular epithelial cells |
| topic | ING2 MRPL12 mitochondrial respiration ubiquitination tubular epithelial cells kidney disease |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.700195/full |
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