SREBP1c‐Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells DOI Creative Commons
Xin Wang, Jie Zhou, Yuzhu Peng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality. Accumulating studies suggest mitochondrial dysfunction as the typical characteristics key process of AKI, but underlying mechanism remains elusive. The YME1‐like 1 (YME1L1) ATPase, an inner membrane protein, screened identified to be downregulated in renal tubular epithelial cells various mouse models patients AKI. Dramatically, restoration YME1L1 expression significantly alleviates cisplatin‐induced AKI subsequent chronic disease (CKD) through attenuating via maintaining optic atrophy (OPA1)‐mediated energy metabolism homeostasis. Mechanistically, upregulated sterol regulatory element binding transcription factor 1c (SREBP1c) demonstrated responsible for cisplatin‐mediated transcriptional inhibition directly its promoter region. Moreover, methyltransferase‐like 3 (METTL3)‐mediated m6A modification enhances SREBP1c mRNA stability, thereby upregulating expression. Notably, both depletion tubule‐specific overexpression markedly ameliorate transition CKD. Taken together, these findings that METTL3‐mediated upregulation contributes progression CKD disrupting transcriptionally suppressing YME1L1. Targeting SREBP1c/YME1L1 signaling may serve novel therapeutic strategy against

Language: Английский

SREBP1c‐Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells DOI Creative Commons
Xin Wang, Jie Zhou, Yuzhu Peng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality. Accumulating studies suggest mitochondrial dysfunction as the typical characteristics key process of AKI, but underlying mechanism remains elusive. The YME1‐like 1 (YME1L1) ATPase, an inner membrane protein, screened identified to be downregulated in renal tubular epithelial cells various mouse models patients AKI. Dramatically, restoration YME1L1 expression significantly alleviates cisplatin‐induced AKI subsequent chronic disease (CKD) through attenuating via maintaining optic atrophy (OPA1)‐mediated energy metabolism homeostasis. Mechanistically, upregulated sterol regulatory element binding transcription factor 1c (SREBP1c) demonstrated responsible for cisplatin‐mediated transcriptional inhibition directly its promoter region. Moreover, methyltransferase‐like 3 (METTL3)‐mediated m6A modification enhances SREBP1c mRNA stability, thereby upregulating expression. Notably, both depletion tubule‐specific overexpression markedly ameliorate transition CKD. Taken together, these findings that METTL3‐mediated upregulation contributes progression CKD disrupting transcriptionally suppressing YME1L1. Targeting SREBP1c/YME1L1 signaling may serve novel therapeutic strategy against

Language: Английский

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