SUCLG1 promotes aerobic respiration and progression in plexiform neurofibroma

Zhou,Zifu; Li,Qingfeng; Huo,Ran

doi:10.3892/ijo.2024.5716

SUCLG1 promotes aerobic respiration and progression in plexiform neurofibroma

Authors:
- Zifu Zhou
- Qingfeng Li
- Ran Huo
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Affiliations: Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
Published online on: December 31, 2024 https://doi.org/10.3892/ijo.2024.5716
Article Number: 10
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Plexiform neurofibromas (PNFs) are benign tumors that affect 20‑50% of patients with type I neurofibromatosis (NF1). PNF carries a risk of malignancy. There is no effective cure for PNF. Its onset may be associated with genetic and metabolic abnormalities, but the exact mechanisms remain unclear. Succinate‑CoA ligase GDP/ADP‑Forming Subunit α(SUCLG1), a catalytic enzyme in the tricarboxylic acid cycle, is highly expressed in PNF. The present study aimed to explore the role of SUCLG1 in function and metabolism of PNF cells. SUCLG1 expression was verified using western blotting and immunofluorescence. After inducing SUCLG1 knockdown and overexpression, functional changes in PNF cells were assessed, as well as effects of SUCLG1 on cell respiration and glucose metabolism. Quantitative PCR, WB, electron microscopy and Flow cytometry demonstrated that SUCLG1 enhanced mitochondrial quality and promoted mitochondrial fusion, thereby driving proliferation and migration of tumor cells, inhibiting apoptosis and altering the cell cycle. A Seahorse assay showed that elevated SUCLG1 expression enhanced cell aerobic respiration without affecting the glycolytic process. This suggests that SUCLG1 upregulation in PNF does not trigger the Warburg effect associated with malignant tumors. This study also demonstrated the positive regulation of cellular function by promoting the expression level of the SLC25A1 gene when SUCLG1 expression was elevated. In conclusion, SUCLG1 altered the mechanism of mitochondrial quality control to enhance cell aerobic respiration, thereby driving the pathogenesis of PNF. Thus, SUCLG1 can serve as a potential target in future therapeutic strategies.

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