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Updated: Jul 3, 2026
A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
Machine learning and single-cell analysis identify the mitophagy-associated gene TOMM22 as a potential diagnostic
Yinghao Wu1, Shengting Wu1, Zhiheng Chen1
1Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, PR China.
Background:
Mitophagy selectively eliminates potentially cytotoxic and damaged mitochondria and effectively prevents excessive cytotoxicity from damaged mitochondria, thereby attenuating inflammatory and oxidative responses. However, the potential role of mitophagy in intervertebral disc degeneration remains to be elucidated.
Methods:
The GSVA method, two machine learning methods (SVM-RFE algorithm and random forest), the CIBERSORT and MCPcounter methods, as well as the consensus clustering method and the WGCNA algorithm were used to analyze the involvement of mitophagy in intervertebral disc degeneration, the diagnostic value of mitophagy-associated genes in intervertebral disc degeneration, and the infiltration of immune cells, and identify the gene modules that were closely related to mitophagy. Single-cell analysis was used to detect mitophagy scores and TOMM22 expression, and pseudo-temporal analysis was used to explore the function of TOMM22 in nucleus pulposus cells. In addition, TOMM22 expression was compared between human normal and degenerated intervertebral disc tissue samples by immunohistochemistry and PCR.
Results:
This study identified that the mitophagy pathway score was elevated in intervertebral disc degeneration compared with the normal condition. A strong link was present between mitophagy genes and immune cells, which may be used to typify intervertebral disc degeneration. The single-cell level showed that mitophagy-associated gene TOMM22 was highly expressed in medullary cells of the disease group. Further investigations indicated the upregulation of TOMM22 expression in late-stage nucleus pulposus cells and its role in cellular communication. In addition, human intervertebral disc tissue samples established that TOMM22 levels were higher in disc degeneration samples than in normal samples.
Conclusions:
Our findings revealed that mitophagy may be used in the diagnosis of intervertebral disc degeneration and its typing, and TOMM22 is a molecule in this regard and may act as a potential diagnostic marker in intervertebral disc degeneration.
Insights
Mitophagy, a cellular process, is elevated in intervertebral disc degeneration. The gene TOMM22 is identified as a potential diagnostic marker for this condition.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitophagy selectively removes damaged mitochondria, preventing cellular damage and reducing inflammation.
- The role of mitophagy in intervertebral disc degeneration (IDD) has not been previously understood.
Purpose of the Study:
- To investigate the involvement of mitophagy in IDD.
- To assess the diagnostic value of mitophagy-associated genes in IDD.
- To identify potential biomarkers for IDD.
Main Methods:
- Utilized GSVA, machine learning (SVM-RFE, random forest), CIBERSORT, MCPcounter, consensus clustering, and WGCNA to analyze mitophagy in IDD.
- Performed single-cell and pseudo-temporal analyses to examine mitophagy scores and TOMM22 expression in nucleus pulposus cells.
- Validated TOMM22 expression in human intervertebral disc tissues using immunohistochemistry and PCR.
Main Results:
- Mitophagy pathway scores were significantly higher in IDD compared to normal tissues.
- A strong correlation was found between mitophagy genes and immune cell infiltration, suggesting potential for IDD typing.
- The mitophagy-associated gene TOMM22 was highly expressed in degenerated disc cells and tissues, indicating its role in IDD pathogenesis.
Conclusions:
- Mitophagy plays a significant role in intervertebral disc degeneration.
- TOMM22 is a promising diagnostic marker for intervertebral disc degeneration and may aid in disease classification.
