bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–01–05
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Relationship Between Mitochondrial Biological Function and Breast Cancer: An Approach Based on Mendelian Randomization Analysis.
  2. Mitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation.
  1. Breast J. 2024 ;2024 4434466
    Relationship Between Mitochondrial Biological Function and Breast Cancer: An Approach Based on Mendelian Randomization Analysis.
    Shichen Miao, Qichao Ni, Jun Fang.
      Objective: This study aims to investigate the potential causal link between mitochondrial function and breast cancer using the Mendelian randomization (MR) analysis. Methods: The data used for this study were obtained from genomewide association studies (GWAS) databases on mitochondrial biological function and breast cancer. Mitochondrial function was considered the exposure variable, breast cancer the outcome variable, and specific single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Two MR methods, inverse variance weighting (IVW) and MR-Egger regression, were used to assess the causal association between mitochondrial function and breast cancer. Data analysis and visualization were performed using R software. Results: The results of the analysis revealed that several genes, including 39S ribosomal protein L34, pyruvate carboxylase, rRNA methyltransferase 3, and cytochrome c oxidase assembly factor 3 homolog, are causally linked to an increased risk of breast cancer in European populations. In addition, cytochrome c oxidase subunit 8A and ADP-ribose pyrophosphatase were found to be protective factors against breast cancer in European populations. In East Asian populations, 39S ribosomal protein L52, ATP synthase subunit beta, and pyruvate dehydrogenase (acetyl-transferring) were identified as causal risk factors for breast cancer. Conversely, 39S ribosomal protein L32, ADP-ribose pyrophosphatase, and cytochrome c oxidase subunit 8A were identified as protective factors against breast cancer in this population. Conclusion: In conclusion, this study provides evidence of a causal relationship between mitochondrial function and breast cancer in both European and East Asian populations. Additional research is warranted to further elucidate the mechanisms underlying this association.
    Keywords:  Mendelian randomization; breast cancer; genomewide association studies; mitochondrial function
    DOI:  https://doi.org/10.1155/2024/4434466
  2. Nat Commun. 2025 Jan 02. 16(1): 212
    Mitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation.
    Yong Yi, Guoqiang Wang, Wenhua Zhang, Shuhan Yu, Junjie Fei, Tingting An, Jianqiao Yi, Fengtian Li, Ting Huang, Jian Yang, Mengmeng Niu, Yang Wang, Chuan Xu, Zhi-Xiong Jim Xiao.
      Glucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA. Elevated MT-CO2 increases flavin adenosine dinucleotide (FAD) levels in activating lysine-specific demethylase 1 (LSD1) to epigenetically upregulate JUN transcription, consequently promoting glutaminase-1 (GLS1) and glutaminolysis for tumor cell survival. Furthermore, MT-CO2 is indispensable for oncogenic Ras-induced glutaminolysis and tumor growth, and elevated expression of MT-CO2 is associated with poor prognosis in lung cancer patients. Together, these findings reveal a role for MT-CO2 in adapting to metabolic stress and highlight MT-CO2 as a putative therapeutic target for Ras-driven cancers.
    DOI:  https://doi.org/10.1038/s41467-024-55768-9
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