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Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy

Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromol...

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Autores principales: Criscuolo, Daniela, Avolio, Rosario, Matassa, Danilo Swann, Esposito, Franca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650000/
https://www.ncbi.nlm.nih.gov/pubmed/34888254
http://dx.doi.org/10.3389/fonc.2021.797265
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author Criscuolo, Daniela
Avolio, Rosario
Matassa, Danilo Swann
Esposito, Franca
author_facet Criscuolo, Daniela
Avolio, Rosario
Matassa, Danilo Swann
Esposito, Franca
author_sort Criscuolo, Daniela
collection PubMed
description Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromolecules, from redox modulation to regulation of cell death. Biosynthetic pathways are also heavily affected by the metabolic rewiring, with protein synthesis dysregulation at the hearth of cellular transformation. Accumulating evidence in multiple organisms shows that the metabolic functions of mitochondria are tightly connected to protein synthesis, being assembly and activity of respiratory complexes highly dependent on de novo synthesis of their components. In turn, protein synthesis within the organelle is tightly connected with the cytosolic process. This implies an entire network of interactions and fine-tuned regulations that build up a completely under-estimated level of complexity. We are now only preliminarily beginning to reconstitute such regulatory level in human cells, and to perceive its role in diseases. Indeed, disruption or alterations of these connections trigger conditions of proteotoxic and energetic stress that could be potentially exploited for therapeutic purposes. In this review, we summarize the available literature on the coordinated regulation of mitochondrial and cytosolic mRNA translation, and their effects on the integrity of the mitochondrial proteome and functions. Finally, we highlight the potential held by this topic for future research directions and for the development of innovative therapeutic approaches.
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spelling pubmed-86500002021-12-08 Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy Criscuolo, Daniela Avolio, Rosario Matassa, Danilo Swann Esposito, Franca Front Oncol Oncology Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromolecules, from redox modulation to regulation of cell death. Biosynthetic pathways are also heavily affected by the metabolic rewiring, with protein synthesis dysregulation at the hearth of cellular transformation. Accumulating evidence in multiple organisms shows that the metabolic functions of mitochondria are tightly connected to protein synthesis, being assembly and activity of respiratory complexes highly dependent on de novo synthesis of their components. In turn, protein synthesis within the organelle is tightly connected with the cytosolic process. This implies an entire network of interactions and fine-tuned regulations that build up a completely under-estimated level of complexity. We are now only preliminarily beginning to reconstitute such regulatory level in human cells, and to perceive its role in diseases. Indeed, disruption or alterations of these connections trigger conditions of proteotoxic and energetic stress that could be potentially exploited for therapeutic purposes. In this review, we summarize the available literature on the coordinated regulation of mitochondrial and cytosolic mRNA translation, and their effects on the integrity of the mitochondrial proteome and functions. Finally, we highlight the potential held by this topic for future research directions and for the development of innovative therapeutic approaches. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8650000/ /pubmed/34888254 http://dx.doi.org/10.3389/fonc.2021.797265 Text en Copyright © 2021 Criscuolo, Avolio, Matassa and Esposito https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Criscuolo, Daniela
Avolio, Rosario
Matassa, Danilo Swann
Esposito, Franca
Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title_full Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title_fullStr Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title_full_unstemmed Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title_short Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
title_sort targeting mitochondrial protein expression as a future approach for cancer therapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650000/
https://www.ncbi.nlm.nih.gov/pubmed/34888254
http://dx.doi.org/10.3389/fonc.2021.797265
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