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Lee 2018 Neurol Genet

From Bioblast
Publications in the MiPMap
Lee RG, Sedghi M, Salari M, Shearwood AJ, Stentenbach M, Kariminejad A, Goullee H, Rackham O, Laing NG, Tajsharghi H, Filipovska A (2018) Early-onset Parkinson disease caused by a mutation in CHCHD2 and mitochondrial dysfunction. Neurol Genet 4:e276.

Β» PMID: 30338296 Open Access

Lee RG, Sedghi M, Salari M, Shearwood AJ, Stentenbach M, Kariminejad A, Goullee H, Rackham O, Laing NG, Tajsharghi H, Filipovska A (2018) Neurol Genet

Abstract: Our goal was to identify the gene(s) associated with an early-onset form of Parkinson disease (PD) and the molecular defects associated with this mutation.

We combined whole-exome sequencing and functional genomics to identify the genes associated with early-onset PD. We used fluorescence microscopy, cell, and mitochondrial biology measurements to identify the molecular defects resulting from the identified mutation.

Here, we report an association of a homozygous variant in CHCHD2, encoding coiled-coil-helix-coiled-coil-helix domain containing protein 2, a mitochondrial protein of unknown function, with an early-onset form of PD in a 26-year-old Caucasian woman. The CHCHD2 mutation in PD patient fibroblasts causes fragmentation of the mitochondrial reticular morphology and results in reduced oxidative phosphorylation at complex I and complex IV. Although patient cells could maintain a proton motive force, reactive oxygen species production was increased, which correlated with an increased metabolic rate.

Our findings implicate CHCHD2 in the pathogenesis of recessive early-onset PD, expanding the repertoire of mitochondrial proteins that play a direct role in this disease.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: AU Perth Filipovska A


Labels: MiParea: Respiration, nDNA;cell genetics  Pathology: Parkinson's 

Organism: Human  Tissue;cell: Fibroblast  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS  HRR: Oxygraph-2k 

Labels, 2018-10