Research Progress on NDUFA9 and GBM

Authors

  • Haocheng Jia
  • Qishan Ran

DOI:

https://doi.org/10.54097/gycgdp82

Keywords:

GBM, Complex I, NDUFA9, NDUFA4L2, NDUFA7, Tumor

Abstract

Glioblastoma (GBM) is the most aggressive and deadly malignant glioma of the adult central nervous system (CNS), searching for related genes is very important for the treatment and prognosis of GBM. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 (NDUFA9) is a subunit of NADH: ubiquinone oxidoreductase (complex I), plays a significant rule in oxidative stress and metabolic reprogramming in a range of cancerous malignancies. Recently, it has been proved that NDUFA9 can predict prognosis and immunological status in GBM. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) is a subunit of complex I either which is similar to NDUFA9. Researchers demonstrate that in addition to being significantly upregulated in GBM tissues and cells, increased NDUFA4L2 expression has been found to be a reliable indicator of overall patient survival. Relevant studies on GBM have frequently referred to NDUFA9, as the subunit of the complex I in mitochondria, the mechanism of NDUFA9 on GBM may to do with the activities of mitochondria, oxidative phosphorylation pathway, the electron transfer chain and the production of ROS. However, the specific mechanism of NDUFA9 on GBM still lacks relevant reports and is required for further exploration.

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References

References

[1] Singhal N, Agarwal V. Pediatric gliomatosis cerebri mimicking tubercular encephalitis. J Pediatr Neurosci. 2015. 10(4): 379-81.

[2] Chen R, Smith-Cohn M, Cohen AL, Colman H. Glioma Subclassifications and Their Clinical Significance. Neurotherapeutics. 2017. 14(2): 284-297.

[3] Vasilev A, Sofi R, Rahman R, Smith SJ, Teschemacher AG, Kasparov S. Using Light for Therapy of Glioblastoma Multiforme (GBM). Brain Sci. 2020. 10(2): 75.

[4] Jan CI, Tsai WC, Harn HJ, et al. Predictors of Response to Autologous Dendritic Cell Therapy in Glioblastoma Multiforme. Front Immunol. 2018. 9: 727.

[5] Tykocki T, Eltayeb M. Ten-year survival in glioblastoma. A systematic review. J Clin Neurosci. 2018. 54: 7-13.

[6] van Solinge TS, Nieland L, Chiocca EA, Broekman M. Advances in local therapy for glioblastoma - taking the fight to the tumour. Nat Rev Neurol. 18(4). England:Springer Nature, 2022. 221-236.

[7] Baertling F, Sánchez-Caballero L, van den Brand M, et al. NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect. Clin Genet. 2018. 93(1): 111-118.

[8] Minton DR, Fu L, Mongan NP, Shevchuk MM, Nanus DM, Gudas LJ. Role of NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex 4-Like 2 in Clear Cell Renal Cell Carcinoma. Clin Cancer Res. 2016. 22(11): 2791-801.

[9] Li Z, Sun C, Qin Z. Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming. Theranostics. 2021. 11(17): 8322-8336.

[10] Tello D, Balsa E, Acosta-Iborra B, et al. Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen consumption by inhibiting Complex I activity. Cell Metab. 2011. 14(6): 768-79.

[11] Liu Y, Cai L, Wang H, et al. Novel mitochondrial-related gene signature predicts prognosis and immunological status in glioma. Transl Cancer Res. 2024. 13(7): 3338-3353.

[12] Shteinfer-Kuzmine A, Verma A, Arif T, Aizenberg O, Paul A, Shoshan-Barmaz V. Mitochondria and nucleus cross-talk: Signaling in metabolism, apoptosis, and differentiation, and function in cancer. IUBMB Life. 2021. 73(3): 492-510.

[13] Iranmanesh Y, Jiang B, Favour OC, et al. Mitochondria's Role in the Maintenance of Cancer Stem Cells in Glioblastoma. Front Oncol. 2021. 11: 582694.

[14] Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells. Trends Biochem Sci. 2016. 41(3): 211-218.

[15] Altieri DC. Mitochondria in cancer: clean windmills or stressed tinkerers. Trends Cell Biol. 2023. 33(4): 293-299.

[16] Strickland M, Stoll EA. Metabolic Reprogramming in Glioma. Front Cell Dev Biol. 2017. 5: 43.

[17] Garcia JH, Jain S, Aghi MK. Metabolic Drivers of Invasion in Glioblastoma. Front Cell Dev Biol. 2021. 9: 683276.

[18] Seyfried TN. Cancer as a mitochondrial metabolic disease. Front Cell Dev Biol. 2015. 3: 43.

[19] Virtuoso A, Giovannoni R, De Luca C, et al. The Glioblastoma Microenvironment: Morphology, Metabolism, and Molecular Signature of Glial Dynamics to Discover Metabolic Rewiring Sequence. Int J Mol Sci. 2021. 22(7): 3301.

[20] DeBerardinis RJ, Chandel NS. We need to talk about the Warburg effect. Nat Metab. 2020. 2(2): 127-129.

[21] Weinberg F, Hamanaka R, Wheaton WW, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010. 107(19): 8788-93.

[22] Tan AS, Baty JW, Dong LF, et al. Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab. 2015. 21(1): 81-94.

[23] Ju YS, Alexandrov LB, Gerstung M, et al. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer. Elife. 2014. 3: e02935.

[24] de Beauchamp L, Himonas E, Helgason GV. Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia. Leukemia. 2022. 36(1): 1-12.

[25] Roth KG, Mambetsariev I, Kulkarni P, Salgia R. The Mitochondrion as an Emerging Therapeutic Target in Cancer. Trends Mol Med. 2020. 26(1): 119-134.

[26] Navarro P, Bueno MJ, Zagorac I, et al. Targeting Tumor Mitochondrial Metabolism Overcomes Resistance to Antiangiogenics. Cell Rep. 2016. 15(12): 2705-18.

[27] Kim SH, Li M, Trousil S, et al. Phenformin Inhibits Myeloid-Derived Suppressor Cells and Enhances the Anti-Tumor Activity of PD-1 Blockade in Melanoma. J Invest Dermatol. 2017. 137(8): 1740-1748.

[28] Viale A, Pettazzoni P, Lyssiotis CA, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014. 514(7524): 628-32.

[29] Maher EA, Marin-Valencia I, Bachoo RM, et al. Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed. 2012. 25(11): 1234-44.

[30] Hensley CT, Faubert B, Yuan Q, et al. Metabolic Heterogeneity in Human Lung Tumors. Cell. 2016. 164(4): 681-94.

[31] Zhao RZ, Jiang S, Zhang L, Yu ZB. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med. 2019. 44(1): 3-15.

[32] Gu J, Liu T, Guo R, Zhang L, Yang M. The coupling mechanism of mammalian mitochondrial complex I. Nat Struct Mol Biol. 2022. 29(2): 172-182.

[33] Cheung EC, Vousden KH. The role of ROS in tumour development and progression. Nat Rev Cancer. 2022. 22(5): 280-297.

[34] Park MW, Cha HW, Kim J, et al. NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases. Redox Biol. 2021. 41: 101947.

[35] Wang B, Liu Y, Chen S, et al. A Novel Potentially Causative Variant of NDUFAF7 Revealed by Mutation Screening in a Chinese Family With Pathologic Myopia. Invest Ophthalmol Vis Sci. 2017. 58(10): 4182-4192.

[36] Chen Z, Wei X, Wang X, et al. NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib. Cell Death Dis. 2021. 12(4): 377.

[37] Lee YK, Kwon SM, Lee EB, et al. Mitochondrial Respiratory Defect Enhances Hepatoma Cell Invasiveness via STAT3/ NFE2L1/ STX12 Axis. Cancers (Basel). 2020. 12(9): 2632.

[38] Feng Z, Hom ME, Bearrood TE, et al. Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1. Nat Chem Biol. 2022. 18(10): 1065-1075.

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Published

29-12-2024

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How to Cite

Jia, H., & Ran, Q. (2024). Research Progress on NDUFA9 and GBM. International Journal of Biology and Life Sciences, 8(3), 32-36. https://doi.org/10.54097/gycgdp82