Please use this identifier to cite or link to this item:
Title: Mitochondrial respiratory chain disorganization in Parkinson's disease-relevant PINK1 and DJ1 mutants.
Authors: Lopez-Fabuel, Irene
Martin-Martin, Lucia
Resch-Beusher, Monica
Azkona, Garikoitz
Sanchez-Pernaute, Rosario
Bolaños, Juan P
Keywords: Complexes;DJ1;Human;Mitochondria;Mouse;Neurons;PINK1;Parkinson's disease
metadata.dc.subject.mesh: Animals
Cells, Cultured
Electron Transport Complex I
Mice, Inbred C57BL
Mice, Knockout
Parkinson Disease
Protein Deglycase DJ-1
Protein Kinases
Issue Date: 11-Apr-2017
Abstract: Brain mitochondrial complex I (CI) damage is associated with the loss of the dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD) patients. However, whether CI inhibition is associated with any alteration of the mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To address this issue, here we analyzed the MRC by blue native gel electrophoresis (BNGE) followed by western blotting, in mitochondria purified from fibroblasts of patients harboring PD-relevant Pink1 mutations. We found a decrease in free CI, and in free versus supercomplexes (SCs)-assembled CI in PD; however, free complex III (CIII) was only modestly affected, whereas its free versus SCs-assembled forms decreased. Interestingly, complex IV (CIV) was considerably lost in the PD samples. These results were largely confirmed in mitochondria isolated from cultured neurons from Pink1-/- mice, and in cultured neurons and forebrain samples from the PD-related Dj1-/- mice. Thus, besides CI damage, the MRC undergoes a profound structural remodeling in PD likely responsible for the energetic inefficiency and mitochondrial reactive oxygen species (mROS) over-production observed in this disease.
metadata.dc.identifier.doi: 10.1016/j.neuint.2017.03.023
Appears in Collections:Producción 2020

Files in This Item:
There are no files associated with this item.

This item is protected by original copyright

Except where otherwise noted, Items on the Andalusian Health Repository site are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives License.