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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380824/ https://www.ncbi.nlm.nih.gov/pubmed/34434929 http://dx.doi.org/10.3389/fcell.2021.700195 |
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author | Yang, Ying Li, Chensheng Gu, Xia Zhen, Junhui Zhu, Suwei Lv, Tingting Wan, Qiang Liu, Yi |
author_facet | Yang, Ying Li, Chensheng Gu, Xia Zhen, Junhui Zhu, Suwei Lv, Tingting Wan, Qiang Liu, Yi |
author_sort | Yang, Ying |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8380824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83808242021-08-24 ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells Yang, Ying Li, Chensheng Gu, Xia Zhen, Junhui Zhu, Suwei Lv, Tingting Wan, Qiang Liu, Yi Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-08-09 /pmc/articles/PMC8380824/ /pubmed/34434929 http://dx.doi.org/10.3389/fcell.2021.700195 Text en Copyright © 2021 Yang, Li, Gu, Zhen, Zhu, Lv, Wan and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Yang, Ying Li, Chensheng Gu, Xia Zhen, Junhui Zhu, Suwei Lv, Tingting Wan, Qiang Liu, Yi ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells |
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 | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380824/ https://www.ncbi.nlm.nih.gov/pubmed/34434929 http://dx.doi.org/10.3389/fcell.2021.700195 |
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