A combined proteomics and bioinformatics analysis of ZNHIT1-interacting proteins reveals a significant enrichment in proteins associated with mitochondrial function

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dc.contributor.authorAnantha, Jayanthen
dc.contributor.authorWilson, Fionnuala E.en
dc.contributor.authorMcCarthy, Erinen
dc.contributor.authorMorales-Prieto, Noeliaen
dc.contributor.authorMazzocchi, Martinaen
dc.contributor.authorCollins, Louise M.en
dc.contributor.authorSullivan, Aideen M.en
dc.contributor.authorO'Keeffe, Gerard W.en
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.contributor.funderHORIZON EUROPE Marie Sklodowska-Curie Actionsen
dc.contributor.funderCure Parkinson's Trusten
dc.date.accessioned2024-05-14T14:13:40Z
dc.date.available2024-05-14T14:13:40Z
dc.date.issued2023-05-11en
dc.description.abstractAdenosine 5'-triphosphate (ATP) is the principal source of cellular energy, which is essential for neuronal health and maintenance. Parkinson’s disease (PD) and other neurodegenerative disorders are characterised by impairments in mitochondrial function and reductions in cellular ATP levels. Thus there is a need to better understand the biology of intracellular regulators of ATP production, in order to inform the development of new neuroprotective therapies for diseases such as PD. One such regulator is Zinc finger HIT-domain containing protein 1 (ZNHIT1). ZNHIT1 is an evolutionarily-conserved component of a chromatin-remodelling complex, which has been recently shown to increase cellular ATP production in SH-SY5Y cells and to protect against impairments in mitochondrial function caused by alpha-synuclein, a protein which is integral to PD pathophysiology. This effect of ZNHIT1 on cellular ATP production is thought to be due to increased expression of genes associated with mitochondrial function, but it is also possible that ZNHIT1 regulates mitochondrial function by binding to mitochondrial proteins. To examine this question, we performed a combined proteomics and bioinformatics analysis to identify ZNHIT1-interacting proteins in SH-SY5Y cells. We report that ZNHIT1-interacting proteins are significantly enriched in multiple functional categories, including mitochondrial transport, ATP synthesis and ATP-dependent activity. Furthermore we also report that the correlation between ZNHIT1 and dopaminergic markers is reduced in the PD brain. These data suggest that the reported beneficial effects of ZNHIT1 on ATP production may be mediated, at least in part, by its direct interaction with mitochondrial proteins and suggest that potential alterations in ZNHIT1 in PD may contribute to the known impairments in ATP generation in midbrain dopaminergic neurons in PD.en
dc.description.sponsorshipScience Foundation Ireland (SFIunder grant number 19/FFP/6666); Irish Research Council (GOIPG-2018-2795); HORIZON EUROPE Marie Sklodowska-Curie Actions (Marie Skłodowska-Curie Fellowship programme under grant number MSCA-IF-2019 890290); Cure Parkinson's Trust (grant number CP:GO01)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid102288en
dc.identifier.citationAnantha, J., Wilson, F.E., McCarthy, E., Morales-Prieto, N., Mazzocchi, M., Collins, L.M., Sullivan, A.M. and O’Keeffe, G.W. (2023) ‘A combined proteomics and bioinformatics analysis of ZNHIT1-interacting proteins reveals a significant enrichment in proteins associated with mitochondrial function’, Journal of Chemical Neuroanatomy, 131, 102288 (9 pp). Available at: https://doi.org/10.1016/j.jchemneu.2023.102288.en
dc.identifier.doihttps://doi.org/10.1016/j.jchemneu.2023.102288en
dc.identifier.endpage9en
dc.identifier.issn0891-0618en
dc.identifier.journaltitleJournal of Chemical Neuroanatomyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/15861
dc.identifier.volume131en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.ispartofJournal of Chemical Neuroanatomyen
dc.rights© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectZNHIT1en
dc.subjectProteomicsen
dc.subjectMitochondriaen
dc.subjectParkinson’s diseaseen
dc.subjectDopaminergicen
dc.subjectATPen
dc.titleA combined proteomics and bioinformatics analysis of ZNHIT1-interacting proteins reveals a significant enrichment in proteins associated with mitochondrial functionen
dc.typeArticle (peer-reviewed)en
oaire.citation.volume131en
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