Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain

The existence of sex differences in disease incidence is attributed, in part, to sex differences in metabolism. Uncovering the precise mechanism driving these differences is an extraordinarily complex process influenced by genetics, endogenous hormones, sex-specific lifetime events, individual diffe...

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Detalles Bibliográficos
Autores: McGovern, A.J., Arévalo, María Ángeles, Ciordia, Sergio, García-Segura, Luis M., Barreto, George E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/284966
Acceso en línea:http://hdl.handle.net/10261/284966
Access Level:acceso abierto
Palabra clave:Sex differences
Tibolone
proteome
Mitochondria
respirasome
gonadectomy
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spelling Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the BrainMcGovern, A.J.Arévalo, María ÁngelesCiordia, SergioGarcía-Segura, Luis M.Barreto, George E.Sex differencesTiboloneproteomeMitochondriarespirasomegonadectomyThe existence of sex differences in disease incidence is attributed, in part, to sex differences in metabolism. Uncovering the precise mechanism driving these differences is an extraordinarily complex process influenced by genetics, endogenous hormones, sex-specific lifetime events, individual differences and external environmental/social factors. In fact, such differences may be subtle, but across a life span, increase susceptibility to a pathology. Whilst research persists in the hope of discovering an elegant biological mechanism to underpin sex differences in disease, here, we show, for the first time, that such a mechanism may be subtle in nature but influenced by multiple sex-specific factors. A proteomic dataset was generated from a gonadectomized mouse model treated with Tibolone, a menopausal hormone therapy. Following functional enrichment analysis, we identified that Alzheimer's disease and the electron transport chain-associated pathways were regulated by sex-hormone interactions. Specifically, we identified that the expression of three respirasome proteins, NDUFA2, NDUFA7 and UQCR10, is significantly altered by compounding factors that contribute to sex differences. These proteins function in bioenergetics and produce reactive oxygen species, which are each dysregulated in many diseases with sex differences in incidence. We show sex-specific reprogrammed responses to Tibolone following gonadectomy, which primarily influence the expression of proteins contributing to metabolic pathways. This further infers that metabolic differences may underpin the observed sex differences in disease, but also that hormone therapy research now has potential in exploring sex-specific interventions to produce an effective method of prevention or treatment.This work was partly supported by funding from Science Foundation Ireland under the Frontiers for the Future Programme (Grant #20/FFP-P/8649) to GEB. This work was also supported by grant PID2020-115019RB-I00, awarded to M.A.A., from Agencia Estatal de Investigación (AEI), co-funded by Fondo Europeo de Desarrollo Regional (FEDER) and by Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.Molecular Diversity Preservation InternationalScience Foundation IrelandAgencia Estatal de Investigación (España)European CommissionCentro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/284966reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115019RB-I00http://dx.doi.org/10.3390/ijms232314754Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2849662026-05-22T06:33:51Z
dc.title.none.fl_str_mv Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
title Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
spellingShingle Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
McGovern, A.J.
Sex differences
Tibolone
proteome
Mitochondria
respirasome
gonadectomy
title_short Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
title_full Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
title_fullStr Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
title_full_unstemmed Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
title_sort Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
dc.creator.none.fl_str_mv McGovern, A.J.
Arévalo, María Ángeles
Ciordia, Sergio
García-Segura, Luis M.
Barreto, George E.
author McGovern, A.J.
author_facet McGovern, A.J.
Arévalo, María Ángeles
Ciordia, Sergio
García-Segura, Luis M.
Barreto, George E.
author_role author
author2 Arévalo, María Ángeles
Ciordia, Sergio
García-Segura, Luis M.
Barreto, George E.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Science Foundation Ireland
Agencia Estatal de Investigación (España)
European Commission
Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Sex differences
Tibolone
proteome
Mitochondria
respirasome
gonadectomy
topic Sex differences
Tibolone
proteome
Mitochondria
respirasome
gonadectomy
description The existence of sex differences in disease incidence is attributed, in part, to sex differences in metabolism. Uncovering the precise mechanism driving these differences is an extraordinarily complex process influenced by genetics, endogenous hormones, sex-specific lifetime events, individual differences and external environmental/social factors. In fact, such differences may be subtle, but across a life span, increase susceptibility to a pathology. Whilst research persists in the hope of discovering an elegant biological mechanism to underpin sex differences in disease, here, we show, for the first time, that such a mechanism may be subtle in nature but influenced by multiple sex-specific factors. A proteomic dataset was generated from a gonadectomized mouse model treated with Tibolone, a menopausal hormone therapy. Following functional enrichment analysis, we identified that Alzheimer's disease and the electron transport chain-associated pathways were regulated by sex-hormone interactions. Specifically, we identified that the expression of three respirasome proteins, NDUFA2, NDUFA7 and UQCR10, is significantly altered by compounding factors that contribute to sex differences. These proteins function in bioenergetics and produce reactive oxygen species, which are each dysregulated in many diseases with sex differences in incidence. We show sex-specific reprogrammed responses to Tibolone following gonadectomy, which primarily influence the expression of proteins contributing to metabolic pathways. This further infers that metabolic differences may underpin the observed sex differences in disease, but also that hormone therapy research now has potential in exploring sex-specific interventions to produce an effective method of prevention or treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
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/10261/284966
url http://hdl.handle.net/10261/284966
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115019RB-I00
http://dx.doi.org/10.3390/ijms232314754
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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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