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...
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| Published in | Psychiatry research Vol. 236; pp. 148 - 157 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Ireland
Elsevier B.V
28.02.2016
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| Abstract | 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. |
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| AbstractList | 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.
•PARK-7, STAT3, SIRT-3, and IMP-2 play an important role in regulating complex I activity.•Published microarray data revealed trend towards downregulation of PARK-7 in patients with BD.•Immunocontent of DJ-1 was not increased in post-mortem prefrontal cortex from patients with BD. 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. 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. |
| Author | Ceylan, Deniz Andreazza, Ana C Berk, Michael Duong, Angela Che, Yi Trevor Young, L Pinguelo, Arsene |
| Author_xml | – sequence: 1 fullname: Duong, Angela – sequence: 2 fullname: Che, Yi – sequence: 3 fullname: Ceylan, Deniz – sequence: 4 fullname: Pinguelo, Arsene – sequence: 5 fullname: Andreazza, Ana C – sequence: 6 fullname: Trevor Young, L – sequence: 7 fullname: Berk, Michael |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26723136$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3389_fgene_2021_636294 crossref_primary_10_1176_appi_ajp_2020_19111210 crossref_primary_10_1093_ijnp_pyy014 crossref_primary_10_1159_000484348 crossref_primary_10_1038_s41398_020_01046_3 crossref_primary_10_1038_mp_2016_123 crossref_primary_10_1016_j_pharmthera_2022_108279 |
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| Keywords | 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 |
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| Snippet | Abstract Phenomenologically, bipolar disorder (BD) is characterized by biphasic increases and decreases in energy. As this is a state-related phenomenon,... Phenomenologically, bipolar disorder (BD) is characterized by biphasic increases and decreases in energy. As this is a state-related phenomenon, identifying... |
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| SubjectTerms | 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 |
| Title | Regulators of mitochondrial complex I activity: A review of literature and evaluation in postmortem prefrontal cortex from patients with bipolar disorder |
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