2. Academic Validation
  3. NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma

NDUFS3 promotes proliferation via glucose metabolism reprogramming inducing AMPK phosphorylating PRPS1 to increase the purine nucleotide synthesis in melanoma

  • Cell Death Differ. 2025 May 22. doi: 10.1038/s41418-025-01525-4.
Guohang Xiong 1 2,  Fang Yun 1,  Lu Jiang 1 3,  Zihan Yi 1 4,  Xiaojia Yi 1 5,  Lijuan Yang 1,  Xuedan Zhang 1,  Xiaoyu Li 1,  Zhe Yang 6,  Qiao Zhang 1,  Buqing Sai 1,  Yingmin Kuang 7,  Yuechun Zhu 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, China.
  • 2 Research Center for Clinical Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, China.
  • 3 Department of Pathology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, 210000, China.
  • 4 Department of Medical Oncology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China.
  • 5 Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 434000, China.
  • 6 Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, China.
  • 7 Department of Organ Transplantation, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. yingmin1512@aliyun.com.
  • 8 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, China. zhuyuechun20091119@163.com.
PMID: 40404919 DOI: 10.1038/s41418-025-01525-4
Abstract

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) is the core subunit of the respiratory chain complex I (CI). We found NDUFS3 were abnormally elevated in human melanoma and promoted melanoma proliferation. Furthermore, NDUFS3 could promote the Oxidative Phosphorylation (OXPHOS) and the pentose phosphate pathway (PPP), as well as attenuated glycolysis. As NDUFS3-mediated the metabolic changes of OXPHOS and glucose metabolism, melanoma cells produced more ATP, resulting in the inhibition of AMP kinase (AMPK). AMPK induced phosphoribosyl pyrophosphate synthetase1 (PRPS1) phosphorylation, which resulted in suppressed PRPS1 activity. Briefly, the NDUFS3-AMPK-PRPS1 signaling axis coupled OXPHOS, glucose metabolism, and purine nucleotide biosynthesis to regulate melanoma proliferation. Our study highlighted an unrecognized role for NDUFS3 in melanoma, which might be used as a potential therapeutic target for the treatment of this type of Cancer. NDUFS3 regulating PRPS1 activity through AMPK to affect melanoma proliferation.

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