Published online Nov 19, 2021. doi: 10.5498/wjp.v11.i11.1075
Peer-review started: April 25, 2021
First decision: July 14, 2021
Revised: July 26, 2021
Accepted: August 25, 2021
Article in press: August 25, 2021
Published online: November 19, 2021
Processing time: 205 Days and 10.4 Hours
Schizophrenia afflicts 1% of the world population. Clinical studies suggest that schizophrenia patients may have an imbalance of mitochondrial energy metabolism via inhibition of mitochondrial complex I activity. Moreover, recent studies have shown that ERVWE1 is also a risk factor for schizophrenia. Nevertheless, there is no available literature concerning the relationship between complex I deficits and ERVWE1 in schizophrenia. Identifying risk factors and blood-based biomarkers for schizophrenia may provide new guidelines for early interventions and prevention programs.
To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia.
Quantitative polymerase chain reaction (qPCR) and enzyme-linked immuno
Herein, we reported decreasing levels of CPEB1 and NDUFV2 in schizophrenia patients. Further studies showed that ERVWE1 was negatively correlated with CPEB1 and NDUFV2 in schizophrenia. Moreover, NDUFV2P1 was increased and demonstrated a significant positive correlation with ERVWE1 and a negative correlation with NDUFV2 in schizophrenia. In vitro experiments disclosed that ERVWE1 suppressed NDUFV2 expression and promoter activity by increasing NDUFV2P1 level. The luciferase assay revealed that ERVWE1 could enhance the promoter activity of NDUFV2P1. Additionally, ERVWE1 downregulated the expression of CPEB1 by suppressing the promoter activity, and the 400 base pair sequence at the 3′ terminus of the promoter was the minimum sequence required. Advanced studies showed that CPEB1 participated in regulating the NDUFV2P1/NDUFV2 axis mediated by ERVWE1. Finally, we found that ERVWE1 inhibited complex I activity in SH-SY5Y cells via the CPEB1/NDUF
In conclusion, CPEB1 and NDUFV2 might be novel potential blood-based biomarkers and pathogenic factors in schizophrenia. Our findings also reveal a novel mechanism of ERVWE1 in the etiology of schizophrenia.
Core Tip: Schizophrenia is a devastating psychiatric disorder. Clinical studies suggest complex I deficits and abnormal expression of ERVWE1 in schizophrenia. We found that CPEB1 might be a novel blood-based biomarker for schizophrenia. Analyses indicated that ERVWE1 was negatively correlated with CPEB1 and NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2) in schizophrenia patients. CPEB1 functioned as a mediator of the NDUFV2 pseudogene (NDUFV2P1)/NDUFV2 pathway induced by ERVWE1. Moreover, ERVWE1 inhibited complex I activity via the CPEB1/NDUFV2P1/NDUFV2 pathway. Thus, CPEB1 and NDUFV2 may be independent risk factors for schizophrenia. Our findings also reveal the role of ERVWE1 in modulating mitochondrial energy metabolism in schizophrenia.