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Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia
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SYSNO ASEP 0579544 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia Tvůrce(i) Kolář, D. (CZ)
Krajčovič, Branislav (FGU-C) ORCID
Kletečková, L. (CZ)
Kunčická, Daniela (FGU-C) ORCID
Valeš, K. (CZ)
Brožka, Hana (FGU-C) ORCID, SAI, RIDZdroj.dok. Schizophrenia Bulletin - ISSN 0586-7614
Roč. 49, č. 6 (2023), s. 1637-1653Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova energy metabolism ; 22q11.2DS ; schizophrenia ; mitochondria Obor OECD Neurosciences (including psychophysiology CEP GA22-15096S GA ČR - Grantová agentura ČR NU22J-04-00061 GA MZd - Ministerstvo zdravotnictví Způsob publikování Omezený přístup Institucionální podpora FGU-C - RVO:67985823 UT WOS 001015893700001 EID SCOPUS 85178499492 DOI 10.1093/schbul/sbad066 Anotace Background and Hypothesis Schizophrenia is associated with altered energy metabolism, but the cause and potential impact of these metabolic changes remain unknown. 22q11.2 deletion syndrome (22q11.2DS) represents a genetic risk factor for schizophrenia, which is associated with the loss of several genes involved in mitochondrial physiology. Here we examine how the haploinsufficiency of these genes could contribute to the emergence of schizophrenia in 22q11.2DS. Study Design We characterize changes in neuronal mitochondrial function caused by haploinsufficiency of mitochondria-associated genes within the 22q11.2 region (PRODH, MRPL40, TANGO2, ZDHHC8, SLC25A1, TXNRD2, UFD1, and DGCR8). For that purpose, we combine data from 22q11.2DS carriers and schizophrenia patients, in vivo (animal models) and in vitro (induced pluripotent stem cells, IPSCs) studies. We also review the current knowledge about seven non-coding microRNA molecules located in the 22q11.2 region that may be indirectly involved in energy metabolism by acting as regulatory factors. Study Results We found that the haploinsufficiency of genes of interest is mainly associated with increased oxidative stress, altered energy metabolism, and calcium homeostasis in animal models. Studies on IPSCs from 22q11.2DS carriers corroborate findings of deficits in the brain energy metabolism, implying a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS. Conclusions The haploinsufficiency of genes within the 22q11.2 region leads to multifaceted mitochondrial dysfunction with consequences to neuronal function, viability, and wiring. Overlap between in vitro and in vivo studies implies a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2024 Elektronická adresa https://doi.org/10.1093/schbul/sbad066
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