RT Journal Article
T1 Mitochondrial respiratory chain disorganization in Parkinson's disease-relevant PINK1 and DJ1 mutants.
A1 Lopez-Fabuel, Irene
A1 Martin-Martin, Lucia
A1 Resch-Beusher, Monica
A1 Azkona, Garikoitz
A1 Sanchez-Pernaute, Rosario
A1 Bolaños, Juan P
K1 Complexes
K1 DJ1
K1 Human
K1 Mitochondria
K1 Mouse
K1 Neurons
K1 PINK1
K1 Parkinson's disease
AB 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.
YR 2017
FD 2017-04-11
LK http://hdl.handle.net/10668/11092
UL http://hdl.handle.net/10668/11092
LA en
DS RISalud
RD Apr 7, 2025