Mitochondrial cholesterol: Metabolism and impact on redox biology and disease

Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cho...

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Detalles Bibliográficos
Autores: Goicoechea, Leire, Torres, Sandra, García-Ruiz, Carmen, Fernández-Checa, José C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/337796
Acceso en línea:http://hdl.handle.net/10261/337796
Access Level:acceso abierto
Palabra clave:Mitochondria
Cholesterol
ROS
Metabolism
Liver disease
Neurodegeneration
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spelling Mitochondrial cholesterol: Metabolism and impact on redox biology and diseaseGoicoechea, LeireTorres, SandraGarcía-Ruiz, CarmenFernández-Checa, José C.MitochondriaCholesterolROSMetabolismLiver diseaseNeurodegenerationCholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cholesterol in the inner mitochondrial membrane (IMM), the metabolism of cholesterol in the IMM plays important physiological roles, acting as the precursor for the synthesis of steroid hormones and neurosteroids in steroidogenic tissues and specific neurons, respectively, or the synthesis of bile acids through an alternative pathway in the liver. Accumulation of cholesterol in mitochondria above physiological levels has a negative impact on mitochondrial function through several mechanisms, including the limitation of crucial antioxidant defenses, such as the glutathione redox cycle, increased generation of reactive oxygen species and consequent oxidative modification of cardiolipin, and defective assembly of respiratory supercomplexes. These adverse consequences of increased mitochondrial cholesterol trafficking trigger the onset of oxidative stress and cell death, and, ultimately, contribute to the development of diverse diseases, including metabolic liver diseases (i.e. fatty liver disease and liver cancer), as well as lysosomal disorders (i.e. Niemann-Pick type C disease) and neurodegenerative diseases (i.e. Alzheimer's disease). In this review, we summarize the metabolism and regulation of mitochondrial cholesterol and its potential impact on liver and neurodegenerative diseases.We acknowledge the support from grants PID2019-111669RB-100 and PID2020-115055RB-I00 from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER) and from the CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017- 1112, European Cooperation in Science & Technology (COST) ACTION CA17112, Prospective European Drug- Induced Liver Injury Network, the 2018-102799-T “Enfermedades Metabólicas y Cancer” from the Red Nacional of the Spanish Health Ministry and the Project 201916/31 Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis 2019 by Fundació Marató TV3. In addition, this project has received funding from the European Horizon's research and innovation program HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679.Peer reviewedElsevierAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionCentro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)Fundació La Marató de TV3Generalitat de CatalunyaNational Institute on Alcohol Abuse and Alcoholism (US)National Institutes of Health (US)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/337796reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111669RB-I00info:eu-repo/grantAgreement/EC/HE/101095679http://dx.doi.org/10.1016/j.redox.2023.102643Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3377962026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
title Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
spellingShingle Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
Goicoechea, Leire
Mitochondria
Cholesterol
ROS
Metabolism
Liver disease
Neurodegeneration
title_short Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
title_full Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
title_fullStr Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
title_full_unstemmed Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
title_sort Mitochondrial cholesterol: Metabolism and impact on redox biology and disease
dc.creator.none.fl_str_mv Goicoechea, Leire
Torres, Sandra
García-Ruiz, Carmen
Fernández-Checa, José C.
author Goicoechea, Leire
author_facet Goicoechea, Leire
Torres, Sandra
García-Ruiz, Carmen
Fernández-Checa, José C.
author_role author
author2 Torres, Sandra
García-Ruiz, Carmen
Fernández-Checa, José C.
author2_role author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)
Fundació La Marató de TV3
Generalitat de Catalunya
National Institute on Alcohol Abuse and Alcoholism (US)
National Institutes of Health (US)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Mitochondria
Cholesterol
ROS
Metabolism
Liver disease
Neurodegeneration
topic Mitochondria
Cholesterol
ROS
Metabolism
Liver disease
Neurodegeneration
description Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cholesterol in the inner mitochondrial membrane (IMM), the metabolism of cholesterol in the IMM plays important physiological roles, acting as the precursor for the synthesis of steroid hormones and neurosteroids in steroidogenic tissues and specific neurons, respectively, or the synthesis of bile acids through an alternative pathway in the liver. Accumulation of cholesterol in mitochondria above physiological levels has a negative impact on mitochondrial function through several mechanisms, including the limitation of crucial antioxidant defenses, such as the glutathione redox cycle, increased generation of reactive oxygen species and consequent oxidative modification of cardiolipin, and defective assembly of respiratory supercomplexes. These adverse consequences of increased mitochondrial cholesterol trafficking trigger the onset of oxidative stress and cell death, and, ultimately, contribute to the development of diverse diseases, including metabolic liver diseases (i.e. fatty liver disease and liver cancer), as well as lysosomal disorders (i.e. Niemann-Pick type C disease) and neurodegenerative diseases (i.e. Alzheimer's disease). In this review, we summarize the metabolism and regulation of mitochondrial cholesterol and its potential impact on liver and neurodegenerative diseases.
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_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/337796
url http://hdl.handle.net/10261/337796
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111669RB-I00
info:eu-repo/grantAgreement/EC/HE/101095679
http://dx.doi.org/10.1016/j.redox.2023.102643
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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