title: Regulators of mitochondrial complex I activity: A review of literature and evaluation in postmortem prefrontal cortex from patients with bipolar disorder.
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.
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Duong
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Che
authors.affiliation: Department of Psychiatry, Gümüşhane State Hospital, Gümüşhane, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ceylan
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Arsene
authors.initials: A
authors.lastname: Pinguelo
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Trevor Young
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong 3220, Australia; Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, the Department of Psychiatry and the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Parkville, Australia. Electronic address: MIKEBE@BarwonHealth.org.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001344:Autopsy; D001714:Bipolar Disorder / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D016601:RNA-Binding Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D056566:Sirtuin 3 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C498779:IGF2BP2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: Bipolar disorder; DJ-1; Gene expression; Microarray; Mitochondrial complex I; Mitochondrial regulators