Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F23%3A43921150" target="_blank" >RIV/00023752:_____/23:43921150 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/23:00579544 RIV/00216208:11120/23:43925833
Result on the web
<a href="https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.1093/schbul/sbad066/7209627?login=true" target="_blank" >https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.1093/schbul/sbad066/7209627?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/schbul/sbad066" target="_blank" >10.1093/schbul/sbad066</a>
Alternative languages
Result language
angličtina
Original language name
Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia
Original language description
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. 22q11.2 deletion syndrome leads to changes in energy metabolism: Lower ATP levels, enhanced glycolysis and decreased OXPHOS rates, decreased antioxidant capacity, and aberrant calcium homeostasis. Although 22q11.2DS is the strongest single genetic risk factor for schizophrenia development, prenatal or postnatal insults (as indicated by the second hit) are necessary for schizophrenia to develop.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30215 - Psychiatry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Schizophrenia Bulletin
ISSN
0586-7614
e-ISSN
1745-1701
Volume of the periodical
49
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
1637-1653
UT code for WoS article
001015893700001
EID of the result in the Scopus database
2-s2.0-85178499492