Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1862, Issue 4, Pages 741-753Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2016.01.022
Keywords
Mitochondrial membrane viscosity; OxPhos supercomplex assembly; Neurodegeneration; Parkinson's disease; Compensatory processes
Funding
- Statutory Funds of the Institute of Pharmacology, Polish Academy of Sciences in Krakow, Poland
- DAAD scholarship [A/12/05080]
- DAAD joint program promoting Polish-German Personnel Exchange [56270132]
- MOBILNOSC PLUS scholarship - Polish MNiSW [904/MOB/2012/0]
- Technische Universitat Darmstadt
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In Parkinson's disease (PD) motor symptoms are not observed until loss of 70% of dopaminergic neurons in substantia nigra (SN), preventing early diagnosis. Mitochondrial dysfunction was indicated in neuropathological process already at early PD stages. Aging and oxidative stress, the main factors in PD pathogenesis, cause membrane stiffening, which could influence functioning of membrane-bound oxidative phosphorylation (OxPhos) complexes (Cxs) in mitochondria. In 6-OHDA rat model, medium-sized dopaminergic lesion was used to study mitochondrial membrane viscosity and changes at the level of OxPhos Cxs and their higher assembled states-supercomplexes (SCxs), during the early degeneration processes and after it. We observed loss of dopaminergic phenotype in SN and decreased dopamine level in striatum (STR) before actual death of neurons in SN. Behavioural deficits induced by lesion were reversed despite progressing neurodegeneration. Along with degeneration process in STR, mitochondrial Cx I performance and amount decreased in almost all forms of SCxs. Also, progressing decrease of Cx IV performance in SCxs (I1III2IV3-1, I1IV2-1) in STR was observed during degeneration. In SN, SCxs containing Cx I increased protein amount and a shifted individual Cx I-1 into superassembled states. Importantly, mitochondria( membrane viscosity changed in parallel with altered SCxs performance. We show for the first time changes at the level of mitochondrial membrane viscosity influencing SCxs function after dopaminergic system degeneration. It implicates that altered mitochondrial membrane viscosity could play an important role in regulation of mitochondria functioning and pathomechanisms of PD. The data obtained are also discussed in relation to compensatory processes observed. (C) 2016 Elsevier B.V. All rights reserved.
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