Expression of mitochondria-related genes in lymphoblastoid cells from patients with bipolar disorder
Shinsuke Washizuka1, Chihiro Kakiuchi, Kanako Mori
1Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, Saitama, Japan.
Objectives:
Several studies have suggested mitochondrial abnormality in bipolar disorder. We reported the association of mitochondrial complex I subunit gene, NDUFV2 at 18p11, with bipolar disorder. A decrease in the mRNA expression of this gene was found in patients with bipolar disorder compared with controls. However, it was unclear whether only the NDUFV2 gene exhibited the decreased expression level in bipolar disorder. The aim of this study was to clarify the association of other nuclear-encoded complex I subunit genes and mitochondria-related genes with bipolar disorder.
Methods:
We quantified the mRNA expression level of five nuclear-encoded mitochondrial complex I subunit genes located at the chromosomal regions linked with bipolar disorder other than NDUFV2, three complex IV subunit genes, and four mitochondrial transcription-related genes using a real-time quantitative reverse transcription polymerase chain reaction method in the lymphoblastoid cell lines from 21 patients with bipolar disorder and 11 controls.
Results:
Decreased mRNA expression in patients with bipolar I disorder compared with control subjects was found in most of the complex I subunit genes. In addition, decreased expression levels of these genes correlated with that of NDUFV2. No statistically significant alterations of mRNA expression levels were found between bipolar patients and controls among two of three complex IV subunit genes and all transcription-related genes.
Conclusions:
Our study suggests that the decreased expression of NDUFV2 has a considerable effect on other subunit genes in the mitochondrial respiratory chain and presents further evidence of the biological significance of NDUFV2 in bipolar disorder.
Insights
Bipolar disorder is linked to reduced expression of mitochondrial complex I genes, including NDUFV2. This decrease impacts other genes in the respiratory chain, highlighting NDUFV2
Area of Science:
- Neurogenetics
- Mitochondrial Biology
- Psychiatric Disorders
Background:
- Mitochondrial dysfunction is implicated in bipolar disorder.
- Previous research identified NDUFV2 gene association and decreased mRNA expression in bipolar disorder patients.
- The role of other mitochondrial genes in bipolar disorder remains unclear.
Purpose of the Study:
- To investigate the association of other nuclear-encoded mitochondrial complex I subunit genes and mitochondria-related genes with bipolar disorder.
- To determine if NDUFV2's decreased expression affects other mitochondrial genes in bipolar disorder.
Main Methods:
- Quantified mRNA expression of five nuclear-encoded mitochondrial complex I subunit genes, three complex IV subunit genes, and four mitochondrial transcription-related genes.
- Utilized real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).
- Analyzed lymphoblastoid cell lines from 21 bipolar disorder patients and 11 controls.
Main Results:
- Most investigated complex I subunit genes showed decreased mRNA expression in bipolar I disorder patients compared to controls.
- Decreased expression levels of these complex I genes correlated with NDUFV2 expression.
- No significant alterations were found in complex IV subunit genes or mitochondrial transcription-related genes.
Conclusions:
- Suggests that decreased NDUFV2 expression significantly impacts other mitochondrial respiratory chain subunit genes.
- Provides further evidence for the biological significance of NDUFV2 in bipolar disorder pathogenesis.
- Highlights potential mitochondrial complex I dysfunction as a contributing factor in bipolar disorder.
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