Mitochondrial respiratory chain disorganization in Parkinson's disease-relevant PINK1 and DJ1 mutants. (October 2017)

• Record Type: Journal Article
• Authors: Lopez-Fabuel, Irene; Martin-Martin, Lucia; Resch-Beusher, Monica; Azkona, Garikoitz; Sanchez-Pernaute, Rosario; Bolaños, Juan P.
• Is Part Of: Neurochemistry international. Volume 109(2017)
• Page Start: 101
• Page End: 105
• Publication Date: 2017-10
• Subjects: PINK1 -- DJ1 -- Human -- Mouse -- Neurons -- Parkinson's disease -- Mitochondria -- Complexes; AO with antioxidants -- BNGE blue native gel electrophoresis -- CI complex I -- CIII complex III -- CIV complex IV -- DMEM Dulbecco's Modified Eagle's Medium -- FCS fetal calf serum -- MRC mitochondrial respiratory chain -- mROS mitochondrial reactive oxygen species -- PAGE polyacrylamide gel electrophoresis -- PBS phosphate buffered saline -- Scaf1 supercomplex assembly factor 1 -- SC supercomplex; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.03.023
• Languages: English
• ISSNs: 0197-0186

Abstract

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.