CPEB1, a novel risk gene in recent-onset schizophrenia, contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1
Yaru Xia, Xiao-Cui Wei, Wenshi Li, Qiujin Yan, Xiulin Wu, Wei Yao, Xu-Hang Li, Fan Zhu
Abstract
BACKGROUND: 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. AIM: To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia. METHODS: Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay were used to detect differentially expressed risk factors in blood samples. Clinical statistical analyses were performed by median analyses and Mann-Whitney U analyses. Spearman's rank correlation was applied to examine the correlation between different risk factors in blood samples. qPCR, western blot analysis, and luciferase assay were performed to confirm the relationship among ERVWE1, cytoplasmic polyadenylation element-binding protein 1 (CPEB1), NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), and NDUFV2 pseudogene (NDUFV2P1). The complex I enzyme activity microplate assay was carried out to evaluate the complex I activity induced by ERVWE1. RESULTS: the CPEB1/NDUFV2P1/NDUFV2 signaling pathway. CONCLUSION: 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.