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Title: Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients
Authors: Marques, Ana P. 
Resende, Rosa 
Silva, Diana F. 
Batista, Mariana 
Pereira, Daniela 
Wildenberg, Brigite 
Morais, Sofia 
Macedo, António 
Pais, Claudia 
Melo, Joana B. 
Madeira, Nuno 
Pereira, Cláudia F. 
Keywords: bipolar disorder; mitochondrial dysfunction; mitochondrial biogenesis; mitophagy; bioenergetics; fibroblasts
Issue Date: 7-May-2021
Publisher: MDPI AG
Project: CENTRO-01-0145-FEDER-000012 (HealthyAging2020) 
POCI-01-0145-FEDER-028214 (MAM4BD) 
European Social Fund - Post-Doctoral Researcher Contract SFRH/BPD/101028/2014 
Serial title, monograph or event: Biomedicines
Volume: 9
Issue: 5
Abstract: This study aims to evaluate whether mitochondrial changes occur in the early stages of bipolar disorder (BD). Using fibroblasts derived from BD patients and matched controls, the levels of proteins involved in mitochondrial biogenesis and dynamics (fission and fusion) were evaluated by Western Blot analysis. Mitochondrial membrane potential (MMP) was studied using the fluorescent probe TMRE. Mitochondrial morphology was analyzed with the probe Mitotracker Green and mitophagy was evaluated by quantifying the co-localization of HSP60 (mitochondria marker) and LC3B (autophagosome marker) by immunofluorescence. Furthermore, the activity of the mitochondrial respiratory chain and the glycolytic capacity of controls and BD patients-derived cells were also studied using the Seahorse technology. BD patient-derived fibroblasts exhibit fragmented mitochondria concomitantly with changes in mitochondrial dynamics and biogenesis in comparison with controls. Moreover, a decrease in the MMP and increased mitophagy was observed in fibroblasts obtained from BD patients when compared with control cells. Impaired energetic metabolism due to inhibition of the mitochondrial electron transport chain (ETC) and subsequent ATP depletion, associated with glycolysis stimulation, was also a feature of BD fibroblasts. Overall, these results support the fact that mitochondrial disturbance is an early event implicated in BD pathophysiology that might trigger neuronal changes and modification of brain circuitry.
ISSN: 2227-9059
DOI: 10.3390/biomedicines9050522
Rights: openAccess
Appears in Collections:I&D CIBB - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBIT - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais

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