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https://hdl.handle.net/10316/111824
Title: | Mitochondrial Dysfunction and Decreased Cytochrome c in Cell and Animal Models of Machado-Joseph Disease | Authors: | Almeida, Filipa Ferreira, Ildete L. Naia, Luana Marinho, Daniela Vilaça-Ferreira, Ana Catarina Costa, Marta D. Duarte-Silva, Sara Maciel, Patrícia Rego, A. Cristina |
Keywords: | Machado–Joseph disease; oxygen consumption; calciumhandling; mitochondrial membrane potential; mitochondrial transcription | Issue Date: | 3-Oct-2023 | Publisher: | MDPI | Project: | CENTRO-01-0145-FEDER000012- HealthyAging2020 UIDB/04539/2020 UIDP/04539/2020 LA/P/0058/ 2020 UIDB/50026/2020 UIDP/50026/2020 |
Serial title, monograph or event: | Cells | Volume: | 12 | Issue: | 19 | Abstract: | Mitochondrial dysfunction has been described in many neurodegenerative disorders; however, there is less information regarding mitochondrial deficits in Machado-Joseph disease (MJD), a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ATXN3 gene. In the present study, we characterized the changes in mitochondrial function and biogenesis markers in two MJD models, CMVMJD135 (MJD135) transgenic mice at a fully established phenotype stage and tetracycline-regulated PC6-3 Q108 cell line expressing mutant ataxin-3 (mATXN3). We detected mATXN3 in the mitochondrial fractions of PC6-3 Q108 cells, suggesting the interaction of expanded ATXN3 with the organelle. Interestingly, in both the cerebella of the MJD135 mouse model and in PC6-3 Q108 cells, we found decreased mitochondrial respiration, ATP production and mitochondrial membrane potential, strongly suggesting mitochondrial dysfunction in MJD. Also, in PC6-3 Q108 cells, an additional enhanced glycolytic flux was observed. Supporting the functional deficits observed in MJD mitochondria, MJD135 mouse cerebellum and PC6-3 Q108 cells showed reduced cytochrome c mRNA and protein levels. Overall, our findings show compromised mitochondrial function associated with decreased cytochrome c levels in both cell and animal models of MJD. | URI: | https://hdl.handle.net/10316/111824 | ISSN: | 2073-4409 | DOI: | 10.3390/cells12192397 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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