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:	Daniela Criscuolo, Rosario Avolio, Danilo Swann Matassa, Franca Esposito
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mitochondrial translation protein synthesis inter-organelle coordinated translation regulation mitochondrial protein import mitochondrial protein quality control (mtPQC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d66a2a641d0e497faa8de0e32b64dae5
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spelling	oai:doaj.org-article:d66a2a641d0e497faa8de0e32b64dae52021-11-30T12:34:41ZTargeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy2234-943X10.3389/fonc.2021.797265https://doaj.org/article/d66a2a641d0e497faa8de0e32b64dae52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.797265/fullhttps://doaj.org/toc/2234-943XExtensive 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.Daniela CriscuoloRosario AvolioDanilo Swann MatassaFranca EspositoFrontiers Media S.A.articlemitochondrial translationprotein synthesisinter-organelle coordinated translation regulationmitochondrial protein importmitochondrial protein quality control (mtPQC)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondrial translation protein synthesis inter-organelle coordinated translation regulation mitochondrial protein import mitochondrial protein quality control (mtPQC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mitochondrial translation protein synthesis inter-organelle coordinated translation regulation mitochondrial protein import mitochondrial protein quality control (mtPQC) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Daniela Criscuolo Rosario Avolio Danilo Swann Matassa Franca Esposito Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy
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.
format	article
author	Daniela Criscuolo Rosario Avolio Danilo Swann Matassa Franca Esposito
author_facet	Daniela Criscuolo Rosario Avolio Danilo Swann Matassa Franca Esposito
author_sort	Daniela Criscuolo
title	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_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_sort	targeting mitochondrial protein expression as a future approach for cancer therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d66a2a641d0e497faa8de0e32b64dae5
work_keys_str_mv	AT danielacriscuolo targetingmitochondrialproteinexpressionasafutureapproachforcancertherapy AT rosarioavolio targetingmitochondrialproteinexpressionasafutureapproachforcancertherapy AT daniloswannmatassa targetingmitochondrialproteinexpressionasafutureapproachforcancertherapy AT francaesposito targetingmitochondrialproteinexpressionasafutureapproachforcancertherapy
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Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy

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