2. Academic Validation
  3. NDUFAB1 promotes hepatocellular carcinoma progression by disrupting mitochondrial homeostasis and mitophagy pathway

NDUFAB1 promotes hepatocellular carcinoma progression by disrupting mitochondrial homeostasis and mitophagy pathway

  • Int Immunopharmacol. 2025 Oct 16:167:115664. doi: 10.1016/j.intimp.2025.115664.
Zhaonv Yao 1,  Xianyi Tan 2,  Huanyu Cui 2,  Hongjun Liang 2,  Ating Zhong 2,  Yuxuan Man 2,  Tingzhuang Yi 3,  Zhengbao Zhang 2,  Xuefeng Guo 2,  Shengkui Tan 4,  Xiaonian Zhu 5
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi, China; Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
  • 2 Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi, China.
  • 3 Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Guangxi Higher Education Research Center for Gastrointestinal Microecology and Health Engineering, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Baise City Key Laboratory of Gastrointestinal Microecology and Health, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
  • 4 Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Guangxi Higher Education Research Center for Gastrointestinal Microecology and Health Engineering, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Baise City Key Laboratory of Gastrointestinal Microecology and Health, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China. Electronic address: sktan2008@163.com.
  • 5 Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi, China. Electronic address: zhuxiaonian0403@163.com.
PMID: 41106117 DOI: 10.1016/j.intimp.2025.115664
Abstract

NADH: ubiquinone oxidoreductase subunit AB1 (NDUFAB1), a critical factor of mitochondrial complex I in electron transport chain, is essential for cellular energy metabolism; however, its specific functions and mechanisms in hepatocellular carcinoma (HCC) remain elusive. We found significantly elevated NDUFAB1 expression in HCC tissues, which is correlated significantly with poor patient prognosis and may serve as an independent risk factor (P < 0.05). Loss-of-function experiments revealed that NDUFAB1 knockdown reduced HCC cell proliferation, metastatic potential, and invasive capacity while promoting Apoptosis. Furthermore, NDUFAB1 knockdown led to mitochondrial depolarization, impaired ATP production, and ROS accumulation, concomitant with downregulation of fusion proteins (OPA1, MFN1, MFN2) and upregulation of fission proteins (DRP1, MFF). Transmission electron microscopy revealed mitochondrial fragmentation and increased autolysosomes formation. Transcriptome Sequencing data further indicated that NDUFAB1 may contribute to HCC pathogenesis by disrupting mitochondrial quality control, particularly through modulation of the Mitophagy pathway. Collectively, NDUFAB1 likely promotes HCC progression by disrupting mitochondrial homeostasis, potentially through activation of the Mitophagy pathway. These findings demonstrate that NDUFAB1 may be used as an independent prognostic risk factor in HCC patients.

Keywords

HCC; Mitochondrial homeostasis; Mitophagy; NDUFAB1.

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