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Peer-reviewedCC BY-NC-NDGenome biology

NDUFV1 activation mediates high glucose-induced apoptosis in peritoneal mesothelial cells.

  • Ruolin Li1
  • Ahui Song2
  • Qinqin Wang3
  • Zimeng Li3
  • Yunyao Lin1
  • Ye Tao1
  • Junyan Fang1
  • Pu Li1
  • Chen Li4
  • Yingli Liu5
5 affiliations
  1. 1Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China.
  2. 2Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China.
  3. 3Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
  4. 4Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China. [email protected].
  5. 5Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China. [email protected].
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Abstract

Background

Peritoneal mesothelial cells (PMCs) are critical components of the peritoneum, and prolonged exposure to high glucose in peritoneal dialysis fluid can lead to structural and functional impairment of the peritoneal membrane. However, whether such cellular damage is caused by glucose itself or by the hyperosmotic environment remains controversial.Results

To elucidate the mechanisms underlying high glucose-induced PMCs apoptosis, we obtain the first dynamic proteomic atlas of HMrSV5 cells under different concentration of glouse and mannitol stimulation. After excluding osmosis, 626 differentially expressed proteins are detected following high glucose stimulation. Notably, the up-regulated differentially expressed proteins are significantly enriched in the oxidative phosphorylation pathway, implicating mitochondrial dysfunction in the apoptotic process. Protein-protein interaction network analysis further reveals that NDUFV1, a core subunit of mitochondrial complex I, might be a key regulator. To validate clinical relevance, we perform a comparative proteomic analysis of peritoneal dialysis effluents from new and long-term peritoneal dialysis patients. The clinical proteomics data reveal a marked enrichment of oxidative phosphorylation in the early-stage of dialysis patients, coinciding with notably up-regulation of NDUFV1. Molecular biology experiments demonstrate that the up-regulation of NDUFV1 increases reactive oxygen species production, disrupted mitochondrial membrane potential, thereby promoting apoptosis.Conclusions

In summary, our findings indicate that glucose-based peritoneal dialysis primarily induces mitochondrial oxidative phosphorylation mediated apoptosis of PMCs through high glucose, with NDUFV1 serving as a critical mediator in this process. These results provide new insights into the prevention and treatment of peritoneal dialysis related peritoneal injury.

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Cite

BibTeXRIS
BibTeX
@article{li2026ndufv1,
  title = {{NDUFV1 activation mediates high glucose-induced apoptosis in peritoneal mesothelial cells.}},
  author = {Ruolin Li and Ahui Song and Qinqin Wang and Zimeng Li and Yunyao Lin and Ye Tao and Junyan Fang and Pu Li and Chen Li and Yingli Liu},
  journal = {Genome biology},
  year = {2026},
  month = aug,
  doi = {10.1186/s13059-026-04227-3},
  url = {https://europepmc.org/article/MED/42958544},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - NDUFV1 activation mediates high glucose-induced apoptosis in peritoneal mesothelial cells.
AU  - Ruolin Li
AU  - Ahui Song
AU  - Qinqin Wang
AU  - Zimeng Li
AU  - Yunyao Lin
AU  - Ye Tao
AU  - Junyan Fang
AU  - Pu Li
AU  - Chen Li
AU  - Yingli Liu
PY  - 2026
DA  - 2026/08/03
JO  - Genome biology
DO  - 10.1186/s13059-026-04227-3
UR  - https://europepmc.org/article/MED/42958544
AB  - Background  Peritoneal mesothelial cells (PMCs) are critical components of the peritoneum, and prolonged exposure to high glucose in peritoneal dialysis fluid can lead to structural and functional impairment of the peritoneal membrane. However, whether such cellular damage is caused by glucose itself or by the hyperosmotic environment remains controversial.Results  To elucidate the mechanisms underlying high glucose-induced PMCs apoptosis, we obtain the first dynamic proteomic atlas of HMrSV5 cells under different concentration of glouse and mannitol stimulation. After excluding osmosis, 626 differentially expressed proteins are detected following high glucose stimulation. Notably, the up-regulated differentially expressed proteins are significantly enriched in the oxidative phosphorylation pathway, implicating mitochondrial dysfunction in the apoptotic process. Protein-protein interaction network analysis further reveals that NDUFV1, a core subunit of mitochondrial complex I, might be a key regulator. To validate clinical relevance, we perform a comparative proteomic analysis of peritoneal dialysis effluents from new and long-term peritoneal dialysis patients. The clinical proteomics data reveal a marked enrichment of oxidative phosphorylation in the early-stage of dialysis patients, coinciding with notably up-regulation of NDUFV1. Molecular biology experiments demonstrate that the up-regulation of NDUFV1 increases reactive oxygen species production, disrupted mitochondrial membrane potential, thereby promoting apoptosis.Conclusions  In summary, our findings indicate that glucose-based peritoneal dialysis primarily induces mitochondrial oxidative phosphorylation mediated apoptosis of PMCs through high glucose, with NDUFV1 serving as a critical mediator in this process. These results provide new insights into the prevention and treatment of peritoneal dialysis related peritoneal injury.
SN  - 1474-7596
SN  - 1474-760X
ER  -