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

Angela Duong, Yi Che, Deniz Ceylan, Arsene Pinguelo, Ana C. Andreazza, L. Trevor Young, Michael Berk

Research output: Contribution to journalReview ArticleResearchpeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalPsychiatry Research
Volume236
DOIs
Publication statusPublished - 28 Feb 2016
Externally publishedYes

Keywords

  • Bipolar disorder
  • DJ-1
  • Gene expression
  • Microarray
  • Mitochondrial complex I
  • Mitochondrial regulators

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