Borland 2009 Biochim Biophys Acta

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Borland MK, Mohanakumar KP, Rubinstein JD, Keeney PM, Xie J, Capaldi R, Dunham LD, Trimmer PA, Bennett JP Jr (2009) Relationships among molecular genetic and respiratory properties of Parkinson's disease cybrid cells show similarities to Parkinson's brain tissues. Biochim Biophys Acta 792: 68-74.

» PMID: 18973805 Open Access

Borland MK, Mohanakumar KP, Rubinstein JD, Keeney PM, Xie J, Capaldi R, Dunham LD, Trimmer PA, Bennett JP (2009) Biochim Biophys Acta

Abstract: We have studied sporadic Parkinson's disease (sPD) from expression of patient mitochondrial DNA (mtDNA) in neural cells devoid of their own mtDNA, the "cybrid" model. In spite of reproducing several properties of sPD brain, it remains unclear whether sPD cybrid cells reflect more complex sPD brain bioenergetic pathophysiology. We characterized and correlated respiration of intact sPD cybrid cells with electron transport chain (ETC) protein assembly, complex I ETC gene expression and ETC protein levels in sPD brain. We also assayed expression for multiple ETC genes coded by mtDNA and nuclear DNA (nDNA) in sPD cybrid cells and brain. sPD cybrid cells have reduced levels of mtDNA genes, variable compensatory normalization of mitochondrial gene expression and show robust correlations with mitochondrial ETC gene expression in sPD brains. Relationships among ETC protein levels predict impaired complex I-mediated respiration in sPD brain. That sPD cybrid cells and sPD brain samples show very correlated regulation of nDNA and mtDNA ETC transcriptomes suggests similar bioenergetic physiologies. We propose that further insights into sPD pathogenesis will follow elucidation of mechanisms leading to reduced mtDNA gene levels in sPD cybrids. This will require characterization of the abnormalities and dynamics of mtDNA changes propagated through sPD cybrids over time.

Keywords: Parkinson's disease, Mitochondria, Cybrid, Respiration, Complex I, Gene expression

O2k-Network Lab: US VA Richmond Bennett JP, US VA Richmond Iyer S

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, mt-Medicine  Pathology: Neurodegenerative, Parkinson's 

Organism: Human  Tissue;cell: Nervous system  Preparation: Intact cells  Enzyme: Complex I 

HRR: Oxygraph-2k