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Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins

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 th...

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Autores principales: Avolio, Rosario, Agliarulo, Ilenia, Criscuolo, Daniela, Sarnataro, Daniela, Auriemma, Margherita, Pennacchio, Sara, Calice, Giovanni, Ng, Martin Y., Giorgi, Carlotta, Pinton, Paolo, Cooperman, Barry, Landriscina, Matteo, Esposito, Franca, Matassa, Danilo Swann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882373/
https://www.ncbi.nlm.nih.gov/pubmed/36712063
http://dx.doi.org/10.1101/2023.01.19.524708
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author Avolio, Rosario
Agliarulo, Ilenia
Criscuolo, Daniela
Sarnataro, Daniela
Auriemma, Margherita
Pennacchio, Sara
Calice, Giovanni
Ng, Martin Y.
Giorgi, Carlotta
Pinton, Paolo
Cooperman, Barry
Landriscina, Matteo
Esposito, Franca
Matassa, Danilo Swann
author_facet Avolio, Rosario
Agliarulo, Ilenia
Criscuolo, Daniela
Sarnataro, Daniela
Auriemma, Margherita
Pennacchio, Sara
Calice, Giovanni
Ng, Martin Y.
Giorgi, Carlotta
Pinton, Paolo
Cooperman, Barry
Landriscina, Matteo
Esposito, Franca
Matassa, Danilo Swann
author_sort Avolio, Rosario
collection PubMed
description 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 co-expressed 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.
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spelling pubmed-98823732023-01-28 Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins Avolio, Rosario Agliarulo, Ilenia Criscuolo, Daniela Sarnataro, Daniela Auriemma, Margherita Pennacchio, Sara Calice, Giovanni Ng, Martin Y. Giorgi, Carlotta Pinton, Paolo Cooperman, Barry Landriscina, Matteo Esposito, Franca Matassa, Danilo Swann bioRxiv Article 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 co-expressed 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. Cold Spring Harbor Laboratory 2023-01-19 /pmc/articles/PMC9882373/ /pubmed/36712063 http://dx.doi.org/10.1101/2023.01.19.524708 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Avolio, Rosario
Agliarulo, Ilenia
Criscuolo, Daniela
Sarnataro, Daniela
Auriemma, Margherita
Pennacchio, Sara
Calice, Giovanni
Ng, Martin Y.
Giorgi, Carlotta
Pinton, Paolo
Cooperman, Barry
Landriscina, Matteo
Esposito, Franca
Matassa, Danilo Swann
Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title_full Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title_fullStr Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title_full_unstemmed Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title_short Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins
title_sort cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone trap1 for the synthesis and import of mitochondrial proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882373/
https://www.ncbi.nlm.nih.gov/pubmed/36712063
http://dx.doi.org/10.1101/2023.01.19.524708
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