bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2022‒09‒25
four papers selected by
Gavin McStay
Liverpool John Moores University
  1. The [PSI+] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12.
  2. The phenotypic spectrum of COX20-associated mitochondrial disorder.
  3. COA3 overexpression promotes non-small cell lung cancer metastasis by reprogramming glucose metabolism.
  4. Mitochondrial Protein Cox7b Is a Metabolic Sensor Driving Brain-Specific Metastasis of Human Breast Cancer Cells.
  1. Mol Biol Cell. 2022 Sep 21. mbcE21100499
    The [PSI+] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12.
    Pawan Kumar Saini, Hannah Dawitz, Andreas Aufschnaiter, Stanislav Bondarev, Jinsu Thomas, Amélie Amblard, James Stewart, Nicolas Thierry-Mieg, Martin Ott, Fabien Pierrel.
      Cytochrome c oxidase is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of cytochrome c oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here, experimental evolution of a Saccharomyces cerevisiae Δcox12 strain for ∼300 generations allowed to restore the activity of cytochrome c oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the AAA+ disaggregase Hsp104. Deletion or overexpression of HSP104 also increased respiration of the Δcox12 ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [PSI+] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.
    DOI:  https://doi.org/10.1091/mbc.E21-10-0499
  2. Brain. 2022 Sep 22. pii: awac344. [Epub ahead of print]
    The phenotypic spectrum of COX20-associated mitochondrial disorder.
    Rui Ban, Robert Kopajtich, Junlan Lv, Sarah L Stenton, Masaru Shimura, Zhaoxia Wang, Yun Yuan, Junling Wang, Xiaodi Han, Zhimei Liu, Qiang Shi, Chuanqiang Pu, Holger Prokisch, Fang Fang, Matthias Elstner.
      
    DOI:  https://doi.org/10.1093/brain/awac344
  3. Am J Cancer Res. 2022 ;12(8): 3662-3678
    COA3 overexpression promotes non-small cell lung cancer metastasis by reprogramming glucose metabolism.
    Hongwei Lin, Yanjun Gao, Kang Sun, Qian Zhang, Yujuan Li, Min Chen, Faguang Jin.
      Recent advances in cancer research have revealed a close relationship between mitochondrial dysfunction and cancer development. Human COX assembly factor 3 (COA3), also known as CCDC56, is a mitochondrial transmembrane protein responsible for cytochrome c oxidase (COX) protein complex assembly. However, the clinical implication and biological functions of COA3 remain unexplored in human cancers, including non-small cell lung cancer (NSCLC). Here, we found that COA3 is overexpressed at both mRNA and protein levels in human NSCLC cells, mainly as a result of decreased miR-338-3p level. The protein expression level of COA3 is positively associated with lymph node metastasis and predicts poor survival in patients with NSCLC. Silencing of COA3 significantly attenuated, while forced COA3 expression enhanced the migration and invasiveness of NSCLC cells. Mechanistically, we found that aerobic glycolysis, induced at least in part by dynamic-related protein 1 (DRP1) phosphorylation-mediated mitochondrial fragmentation, contributed to COA3-promoted NSCLC metastasis. Together, our study illustrates that COA3 plays a crucial role in NSCLC carcinogenesis, implying COA3 as a prognostic marker and treatment target in NSCLC.
    Keywords:  COA3; NSCLC; glycolysis; metastasis; mitochondrial fragmentation
  4. Cancers (Basel). 2022 Sep 08. pii: 4371. [Epub ahead of print]14(18):
    Mitochondrial Protein Cox7b Is a Metabolic Sensor Driving Brain-Specific Metastasis of Human Breast Cancer Cells.
    Marine C N M Blackman, Tania Capeloa, Justin D Rondeau, Luca X Zampieri, Zohra Benyahia, Justine A Van de Velde, Maude Fransolet, Evangelos P Daskalopoulos, Carine Michiels, Christophe Beauloye, Pierre Sonveaux.
      Distant metastases are detrimental for cancer patients, but the increasingly early detection of tumors offers a chance for metastasis prevention. Importantly, cancers do not metastasize randomly: depending on the type of cancer, metastatic progenitor cells have a predilection for well-defined organs. This has been theorized by Stephen Paget, who proposed the "seed-and-soil hypothesis", according to which metastatic colonization occurs only when the needs of a given metastatic progenitor cell (the seed) match with the resources provided by a given organ (the soil). Here, we propose to explore the seed-and-soil hypothesis in the context of cancer metabolism, thus hypothesizing that metastatic progenitor cells must be capable of detecting the availability of metabolic resources in order to home in a secondary organ. If true, it would imply the existence of metabolic sensors. Using human triple-negative MDA-MB-231 breast cancer cells and two independent brain-seeking variants as models, we report that cyclooxygenase 7b (Cox7b), a structural component of Complex IV of the mitochondrial electron transport chain, belongs to a probably larger family of proteins responsible for breast cancer brain tropism in mice. For metastasis prevention therapy, this proof-of-principle study opens a quest for the identification of therapeutically targetable metabolic sensors that drive cancer organotropism.
    Keywords:  brain metastasis; breast cancer; cancer metabolism; cyclooxygenase 7b (Cox7b); mitochondria; organotropism; oxidative phosphorylation (OXPHOS); tissue-specific metastasis
    DOI:  https://doi.org/10.3390/cancers14184371
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