mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases

Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most...

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Autores: Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Romero-González, Ana, Suarez-Rivero, Juan M., Romero-Domínguez, José Manuel, Sánchez-Alcázar, José Antonio
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/336881
Acesso em linha:http://hdl.handle.net/10261/336881
Access Level:acceso abierto
Palavra-chave:Mtochondria
Proteostasis
Mitochondrial unfolded protein response
Mitochondrial biogenesis
Therapeutic target
Neurodegenerative diseases
Mitochondrial diseases
Ageing
Metabolic diseases
Cardiovascular diseases
Cancer
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spelling mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial DiseasesCilleros-Holgado, PaulaGómez-Fernández, DavidPiñero-Perez, RocíoReche-López, DianaÁlvarez-Córdoba, MónicaMunuera, ManuelTalaverón-Rey, MartaPovea-Cabello, SulevaSuárez-Carrillo, AlejandraRomero-González, AnaSuarez-Rivero, Juan M.Romero-Domínguez, José ManuelSánchez-Alcázar, José AntonioMtochondriaProteostasisMitochondrial unfolded protein responseMitochondrial biogenesisTherapeutic targetNeurodegenerative diseasesMitochondrial diseasesAgeingMetabolic diseasesCardiovascular diseasesCancerMitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.This project was supported by the FIS PI16/00786 (2016) and FIS PI19/00377 (2019) grants; the Ministerio de Sanidad, Spain; and the Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture, and Sport. This activity was co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge, and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 Thematic objective “01—Reinforcement of research, technological development and innovation” through the reference research project CTS-5725 and PY18-850.Multidisciplinary Digital Publishing InstituteMinisterio de Sanidad (España)European CommissionMinisterio de Educación, Cultura y Deporte (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/336881reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/ijms24021482Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3368812026-05-22T06:33:51Z
dc.title.none.fl_str_mv mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
title mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
spellingShingle mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
Cilleros-Holgado, Paula
Mtochondria
Proteostasis
Mitochondrial unfolded protein response
Mitochondrial biogenesis
Therapeutic target
Neurodegenerative diseases
Mitochondrial diseases
Ageing
Metabolic diseases
Cardiovascular diseases
Cancer
title_short mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
title_full mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
title_fullStr mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
title_full_unstemmed mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
title_sort mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
dc.creator.none.fl_str_mv Cilleros-Holgado, Paula
Gómez-Fernández, David
Piñero-Perez, Rocío
Reche-López, Diana
Álvarez-Córdoba, Mónica
Munuera, Manuel
Talaverón-Rey, Marta
Povea-Cabello, Suleva
Suárez-Carrillo, Alejandra
Romero-González, Ana
Suarez-Rivero, Juan M.
Romero-Domínguez, José Manuel
Sánchez-Alcázar, José Antonio
author Cilleros-Holgado, Paula
author_facet Cilleros-Holgado, Paula
Gómez-Fernández, David
Piñero-Perez, Rocío
Reche-López, Diana
Álvarez-Córdoba, Mónica
Munuera, Manuel
Talaverón-Rey, Marta
Povea-Cabello, Suleva
Suárez-Carrillo, Alejandra
Romero-González, Ana
Suarez-Rivero, Juan M.
Romero-Domínguez, José Manuel
Sánchez-Alcázar, José Antonio
author_role author
author2 Gómez-Fernández, David
Piñero-Perez, Rocío
Reche-López, Diana
Álvarez-Córdoba, Mónica
Munuera, Manuel
Talaverón-Rey, Marta
Povea-Cabello, Suleva
Suárez-Carrillo, Alejandra
Romero-González, Ana
Suarez-Rivero, Juan M.
Romero-Domínguez, José Manuel
Sánchez-Alcázar, José Antonio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Sanidad (España)
European Commission
Ministerio de Educación, Cultura y Deporte (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Mtochondria
Proteostasis
Mitochondrial unfolded protein response
Mitochondrial biogenesis
Therapeutic target
Neurodegenerative diseases
Mitochondrial diseases
Ageing
Metabolic diseases
Cardiovascular diseases
Cancer
topic Mtochondria
Proteostasis
Mitochondrial unfolded protein response
Mitochondrial biogenesis
Therapeutic target
Neurodegenerative diseases
Mitochondrial diseases
Ageing
Metabolic diseases
Cardiovascular diseases
Cancer
description Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/336881
url http://hdl.handle.net/10261/336881
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/ijms24021482

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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