Regulators of mitochondrial complex I activity: A review of literature and evaluation in postmortem prefrontal cortex from patients with bipolar disorder

• Published in: Psychiatry research Vol. 236; pp. 148 - 157
• Main Authors: Duong, Angela, Che, Yi, Ceylan, Deniz, Pinguelo, Arsene, Andreazza, Ana C, Trevor Young, L, Berk, Michael
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.02.2016
• Subjects: Adult; Aged, 80 and over; Autopsy; Bipolar disorder; Bipolar Disorder - genetics; DJ-1; Down-Regulation; Female; Gene expression; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Male; Microarray; Middle Aged; Mitochondrial complex I; Mitochondrial regulators; Oncogene Proteins - metabolism; Prefrontal Cortex - metabolism; Protein Deglycase DJ-1; Psychiatry; RNA-Binding Proteins - metabolism; Sirtuin 3 - metabolism; STAT3 Transcription Factor - metabolism; Up-Regulation; DHEA; NO; BD; flavine mononucleotide; glutathione; dihydroxyphenylacetic acid; Parkinson disease protein 7; 6-OHDA; DJ-1; SCZ; schizophrenia; Microarray; Dehydropiandrosterone; bipolar disorder; insulin-like growth factor 2 [IGF2] mRNA-binding protein 2; reactive oxygen species; STAT-3; Mitochondrial regulators; GSH; nitric oxide; DOPAC 3,4; protein deglycase; FMN; Grx2; glutaredoxin 2; Mitochondrial complex I; PARK-7; signal transducer and activator of transcription 3; Gene expression; 6-hydroxydopamine; ROS; IMP-2; NAD-dependent deacetylase sirtuin; SIRT; Bipolar disorder
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2015.12.015

Abstract Phenomenologically, bipolar disorder (BD) is characterized by biphasic increases and decreases in energy. As this is a state-related phenomenon, identifying regulators responsible for this phasic dysregulation has the potential to uncover key elements in the pathophysiology of BD. Given the evidence suggesting mitochondrial complex I dysfunction in BD, we aimed to identify the main regulators of complex I in BD by reviewing the literature and using the published microarray data to examine their gene expression profiles. We also validated protein expression levels of the main complex I regulators by immunohistochemistry. Upon reviewing the literature, we found PARK-7, STAT-3, SIRT-3 and IMP-2 play an important role in regulating complex I activity. Published microarray studies however revealed no significant direction of regulation of STAT-3 , SIRT-3 , and IMP-2 , but a trend towards downregulation of PARK-7 was observed in BD. Immunocontent of DJ-1 ( PARK-7 -encoded protein) were not elevated in post mortem prefrontal cortex from patients with BD. We also found a trend towards upregulation of DJ-1 expression with age. Our results suggest that DJ-1 is not significantly altered in BD subjects, however further studies are needed to examine DJ-1 expression levels in a cohort of older patients with BD.