Articles producció científica> Medicina i Cirurgia

Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review

  • Dades identificatives

    Identificador: imarina:9243757
    Autors:
    Valiente-Pallejà ATortajada JBulduk BKVilella EGarrabou GMuntané GMartorell L
    Resum:
    Background: Mitochondrial DNA (mtDNA) encodes 37 genes necessary for synthesizing 13 essential subunits of the oxidative phosphorylation system. mtDNA alterations are known to cause mitochondrial disease (MitD), a clinically heterogeneous group of disorders that often present with neuropsychiatric symptoms. Understanding the nature and frequency of mtDNA alterations in health and disease could be a cornerstone in disentangling the relationship between biochemical findings and clinical symptoms of brain disorders. This systematic review aimed to summarize the mtDNA alterations in human brain tissue reported to date that have implications for further research on the pathophysiological significance of mtDNA alterations in brain functioning. Methods: We searched the PubMed and Embase databases using distinct terms related to postmortem human brain and mtDNA up to June 10, 2021. Reports were eligible if they were empirical studies analysing mtDNA in postmortem human brains. Findings: A total of 158 of 637 studies fulfilled the inclusion criteria and were clustered into the following groups: MitD (48 entries), neurological diseases (NeuD, 55 entries), psychiatric diseases (PsyD, 15 entries), a miscellaneous group with controls and other clinical diseases (5 entries), ageing (20 entries), and technical issues (5 entries). Ten entries were ascribed to more than one group. Pathogenic single nucleotide variants (pSNVs), both homo- or heteroplasmic variants, have been widely reported in MitD, with heteroplasmy levels varying among brain regions; however, pSNVs are rarer in NeuD, PsyD and ageing. A lower mtDNA copy number (CN) in disease was described in most, but not all, of the identified studies. mtDNA deletions were identified in individuals in the four clinical categories and
  • Altres:

    Autor segons l'article: Valiente-Pallejà A; Tortajada J; Bulduk BK; Vilella E; Garrabou G; Muntané G; Martorell L
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Bulduk, Bengisu Kevser / Martorell Bonet, Lourdes / Muntané Medina, Gerard / Tortajada Valero, Juan / Valiente Pallejà, Alba / Vilella Cuadrada, Elisabet
    Paraules clau: Stroke-like episodes Psychiatric diseases Postmortem Neurological diseases Mitochondrial dna Mitochondrial diseases Ageing tissue distribution substantia-nigra respiratory-chain parkinsons-disease lactic-acidosis complex i deficiency common deletion alzheimers-disease 4977 bp deletion
    Resum: Background: Mitochondrial DNA (mtDNA) encodes 37 genes necessary for synthesizing 13 essential subunits of the oxidative phosphorylation system. mtDNA alterations are known to cause mitochondrial disease (MitD), a clinically heterogeneous group of disorders that often present with neuropsychiatric symptoms. Understanding the nature and frequency of mtDNA alterations in health and disease could be a cornerstone in disentangling the relationship between biochemical findings and clinical symptoms of brain disorders. This systematic review aimed to summarize the mtDNA alterations in human brain tissue reported to date that have implications for further research on the pathophysiological significance of mtDNA alterations in brain functioning. Methods: We searched the PubMed and Embase databases using distinct terms related to postmortem human brain and mtDNA up to June 10, 2021. Reports were eligible if they were empirical studies analysing mtDNA in postmortem human brains. Findings: A total of 158 of 637 studies fulfilled the inclusion criteria and were clustered into the following groups: MitD (48 entries), neurological diseases (NeuD, 55 entries), psychiatric diseases (PsyD, 15 entries), a miscellaneous group with controls and other clinical diseases (5 entries), ageing (20 entries), and technical issues (5 entries). Ten entries were ascribed to more than one group. Pathogenic single nucleotide variants (pSNVs), both homo- or heteroplasmic variants, have been widely reported in MitD, with heteroplasmy levels varying among brain regions; however, pSNVs are rarer in NeuD, PsyD and ageing. A lower mtDNA copy number (CN) in disease was described in most, but not all, of the identified studies. mtDNA deletions were identified in individuals in the four clinical categories and ageing. Notably, brain samples showed significantly more mtDNA deletions and at higher heteroplasmy percentages than blood samples, and several of the deletions present in the brain were not detected in the blood. Finally, mtDNA heteroplasmy, mtDNA CN and the deletion levels varied depending on the brain region studied. Interpretation: mtDNA alterations are well known to affect human tissues, including the brain. In general, we found that studies of MitD, NeuD, PsyD, and ageing were highly variable in terms of the type of disease or ageing process investigated, number of screened individuals, studied brain regions and technology used. In NeuD and PsyD, no particular type of mtDNA alteration could be unequivocally assigned to any specific disease or diagnostic group. However, the presence of mtDNA deletions and mtDNA CN variation imply a role for mtDNA in NeuD and PsyD. Heteroplasmy levels and threshold effects, affected brain regions, and mitotic segregation patterns of mtDNA alterations may be involved in the complex inheritance of NeuD and PsyD and in the ageing process. Therefore, more information is needed regarding the type of mtDNA alteration, the affected brain regions, the heteroplasmy levels, and their relationship with clinical phenotypes and the ageing process. Funding: Hospital Universitari Institut Pere Mata; Institut d'Investigació Sanitària Pere Virgili; Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI18/00514).
    Àrees temàtiques: Saúde coletiva Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina iii Medicina ii Medicina i General medicine General biochemistry,genetics and molecular biology Ciências biológicas ii Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all)
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: alba.valiente@urv.cat gerard.muntane@urv.cat lourdes.martorell@urv.cat elisabet.vilella@urv.cat juan.tortajada@estudiants.urv.cat bengisukevser.bulduk@estudiants.urv.cat
    Identificador de l'autor: 0000-0003-4999-2197 0000-0002-1887-5919
    Data d'alta del registre: 2024-09-07
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00004-4/fulltext
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Ebiomedicine. 76 103815-
    Referència de l'ítem segons les normes APA: Valiente-Pallejà A; Tortajada J; Bulduk BK; Vilella E; Garrabou G; Muntané G; Martorell L (2022). Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review. Ebiomedicine, 76(), 103815-. DOI: 10.1016/j.ebiom.2022.103815
    DOI de l'article: 10.1016/j.ebiom.2022.103815
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2022
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry, Genetics and Molecular Biology (Miscellaneous),Medicine (Miscellaneous),Medicine, Research & Experimental
    Stroke-like episodes
    Psychiatric diseases
    Postmortem
    Neurological diseases
    Mitochondrial dna
    Mitochondrial diseases
    Ageing
    tissue distribution
    substantia-nigra
    respiratory-chain
    parkinsons-disease
    lactic-acidosis
    complex i deficiency
    common deletion
    alzheimers-disease
    4977 bp deletion
    Saúde coletiva
    Medicine, research & experimental
    Medicine (miscellaneous)
    Medicine (all)
    Medicina iii
    Medicina ii
    Medicina i
    General medicine
    General biochemistry,genetics and molecular biology
    Ciências biológicas ii
    Biotecnología
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
  • Documents:

  • Cerca a google

    Search to google scholar