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DNA-PKcs Interacts with Fis1 Induce Mitochondrial Fragmentation During Acute Kidney Injury

ABSTRACT: To analyze the mechanisms underlying DNA-PKcs deletion-mediated renoprotection in an unbiased fashion, we performed proteomic analysis using label free technology to obtain the protein expression profiles in control and DNA-PKcs-deficient mice subjected to septic AKI. 631 proteins were altered by DNA-PKcs deletion during septic AKI (log2FC>1.5), among which 274 proteins reached statistical difference. An expression volcano map of the differentially expressed proteins showed that 153 proteins were upregulated and 121 were downregulated. Kyoto Encyclopedia of Genes and Genome (KEGG) analysis of the 274 proteins showed that the apoptosis pathway was the most downregulated upon DNA-PKcs deletion during septic AKI. Gene Ontology (GO) Cellular Component Enrichment Analysis demonstrated that 101 of the 274 proteins were enriched to mitochondria

ORGANISM(S): Acyrthosiphon Pisum

SUBMITTER: Hao Zhou

PROVIDER: PXD030271 | iProX | Wed Dec 08 00:00:00 GMT 2021

REPOSITORIES: iProX

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DNA-PKcs interacts with and phosphorylates Fis1 to induce mitochondrial fragmentation in tubular cells during acute kidney injury.

Wang Shiyuan S Zhu Hang H Li Ruibing R Mui David D Toan Sam S Chang Xing X Zhou Hao H

Science signaling 20220315 725

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) regulates cell death. We sought to determine whether DNA-PKcs played a role in the tubular damage that occurs during acute kidney injury (AKI) induced by LPS injection (to mimic sepsis), cisplatin administration, or renal ischemia/reperfusion injury. Although DNA-PKcs normally localizes to the nucleus, we detected cytoplasmic DNA-PKcs in mouse kidney tissues and urinary sediments of human patients with septic AKI. Increased cytopla ...[more]

PMID: 35290083

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