title: Adaptation within mitochondrial oxidative phosphorylation supercomplexes and membrane viscosity during degeneration of dopaminergic neurons in an animal model of early Parkinson's disease.
abstract: 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 I1 into superassembled states. Importantly, mitochondrial 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.
authors: Department of Neuropsychopharmacology, Polish Academy of Sciences, Smętna St. 12, 31-343 Kraków, Poland. Electronic address: kuter@if-pan.krakow.pl.
authors: Katarzyna
authors: K
authors: Kuter
authors: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany.
authors: Manuela
authors: M
authors: Kratochwil
authors: Department of Neuropsychopharmacology, Polish Academy of Sciences, Smętna St. 12, 31-343 Kraków, Poland.
authors: Klemencja
authors: K
authors: Berghauzen-Maciejewska
authors: Department of Neuropsychopharmacology, Polish Academy of Sciences, Smętna St. 12, 31-343 Kraków, Poland.
authors: Urszula
authors: U
authors: Głowacka
authors: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany; Clinical Neurobiology, Charité-Universitätsmedizin, D-12203 Berlin, Germany.
authors: Michiru D
authors: MD
authors: Sugawa
authors: Department of Neuropsychopharmacology, Polish Academy of Sciences, Smętna St. 12, 31-343 Kraków, Poland.
authors: Krystyna
authors: K
authors: Ossowska
authors: Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany.
authors: Norbert A
authors: NA
authors: Dencher
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D016627:Oxidopamine / Q000009:adverse effects* / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D024101:Mitochondrial Proteins; D016627:Oxidopamine
keywords: Compensatory processes; Mitochondrial membrane viscosity; Neurodegeneration; OxPhos supercomplex assembly; Parkinson's disease