bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2023–07–30
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer.
  2. Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.
  1. Genes (Basel). 2023 Jul 18. pii: 1465. [Epub ahead of print]14(7):
    Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer.
    Ricardo Cunha de Oliveira, Sávio Pinho Dos Reis, Giovanna C Cavalcante.
      Although it has gained more attention in recent years, the relationship between breast cancer (BC) and mitochondrial oxidative phosphorylation (OXPHOS) is still not well understood. Importantly, Complex IV or Cytochrome C Oxidase (COX) of OXPHOS is one of the key players in mitochondrial balance. An in silico investigation of mutations in structural genes of Complex IV was conducted in BC, comprising 2107 samples. Our findings show four variants (rs267606614, rs753969142, rs199476128 and rs267606884) with significant pathogenic potential. Moreover, we highlight nine genes (MT-CO1, MT-CO2, MT-CO3, CO4I2, COX5A, COX5B, COX6A2, COX6C and COX7B2) with a potential impact on BC.
    Keywords:  breast cancer; complex IV; mitochondria; oxidative phosphorylation
    DOI:  https://doi.org/10.3390/genes14071465
  2. Genome Res. 2023 Jul 24. pii: gr.277755.123. [Epub ahead of print]
    Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.
    Rosario Avolio, Ilenia Agliarulo, Daniela Criscuolo, Daniela Sarnataro, Margherita Auriemma, Sabrina De Lella, Sara Pennacchio, Giovanni Calice, Martin Y Ng, Carlotta Giorgi, Paolo Pinton, Barry Cooperman, Matteo Landriscina, Franca Esposito, Danilo Swann Matassa.
      A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein we identify the molecular mechanisms involved, demonstrating that TRAP1: i) binds both mitochondrial and cytosolic ribosomes as well as translation elongation factors, ii) slows down translation elongation rate, and iii) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration.
    DOI:  https://doi.org/10.1101/gr.277755.123
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