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Mitochondria-related pathogenic genes in acute and chronic kidney disease: a Mendelian randomization study

Jia Wang1, TongLing Yuan1, Qian Wei2

  • 1Department of General Practice Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Renal Failure
|July 9, 2026
PubMed

Insights

This study links mitochondrial genes to kidney diseases using Mendelian randomization. It identified specific genes like ATP23 as risk factors for acute kidney injury (AKI) and chronic kidney disease (CKD).

Area of Science:

  • Genetics and Genomics
  • Mitochondrial Biology
  • Renal Medicine

Background:

  • Mitochondrial dysfunction is implicated in various diseases, including kidney conditions.
  • The genetic links between mitochondrial function and kidney diseases like acute kidney injury (AKI) and chronic kidney disease (CKD) require further elucidation.
  • Understanding these genetic associations can reveal novel therapeutic targets.

Purpose of the Study:

  • To investigate the association between mitochondrial-related genes and the risk of AKI and CKD.
  • To identify specific mitochondrial genes that may act as risk or protective factors for these kidney diseases.
  • To explore the shared genetic pathways underlying AKI and CKD.

Main Methods:

  • Utilized summary-data-based Mendelian randomization (SMR) analysis.
  • Employed mitochondrial-related gene data from MitoCarta3.0 and quantitative trait loci (QTL) data for DNA methylation (mQTLs), gene expression (eQTLs), and protein expression (pQTLs).
  • Performed validation using genome-wide association study summary statistics from the US Million Veteran Program and UK Biobank, alongside kidney cortex-specific eQTL and single-cell transcriptome data.

Main Results:

  • Identified numerous mQTLs, eQTLs, and pQTLs associated with AKI and CKD risk.
  • Discovered shared genetic signals for both AKI and CKD, including genes like FASN, DELE1, SARS2, NDUFB2, and ATP23.
  • Validated ATP23 as a shared risk factor and ATAD3B as a potentially protective factor for CKD in kidney-specific tissues.

Conclusions:

  • Mitochondrial-related genes play a significant role in the pathogenesis of both AKI and CKD.
  • Specific genes, such as ATP23 and ATAD3B, represent potential molecular links between mitochondrial function and renal failure.
  • This study provides a genetic basis for understanding mitochondrial involvement in kidney diseases and suggests potential therapeutic targets.
Keywords:
Acute kidney injurychronic kidney diseasecolocalization analysismitochondriasummary-data-based Mendelian randomization

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