PMID- 26844379
OWN - NLM
STAT- MEDLINE
DCOM- 20190328
LR  - 20220317
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1862
IP  - 4
DP  - 2016 Apr
TI  - Adaptation within mitochondrial oxidative phosphorylation supercomplexes and 
      membrane viscosity during degeneration of dopaminergic neurons in an animal model 
      of early Parkinson's disease.
PG  - 741-753
LID - S0925-4439(16)30025-4 [pii]
LID - 10.1016/j.bbadis.2016.01.022 [doi]
AB  - 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.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Kuter, Katarzyna
AU  - Kuter K
AD  - Department of Neuropsychopharmacology, Polish Academy of Sciences, Smetna St. 12, 
      31-343 Krakow, Poland. Electronic address: kuter@if-pan.krakow.pl.
FAU - Kratochwil, Manuela
AU  - Kratochwil M
AD  - Physical Biochemistry, Department of Chemistry, Technische Universitat Darmstadt, 
      Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany.
FAU - Berghauzen-Maciejewska, Klemencja
AU  - Berghauzen-Maciejewska K
AD  - Department of Neuropsychopharmacology, Polish Academy of Sciences, Smetna St. 12, 
      31-343 Krakow, Poland.
FAU - Glowacka, Urszula
AU  - Glowacka U
AD  - Department of Neuropsychopharmacology, Polish Academy of Sciences, Smetna St. 12, 
      31-343 Krakow, Poland.
FAU - Sugawa, Michiru D
AU  - Sugawa MD
AD  - Physical Biochemistry, Department of Chemistry, Technische Universitat Darmstadt, 
      Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany; Clinical Neurobiology, 
      Charite-Universitatsmedizin, D-12203 Berlin, Germany.
FAU - Ossowska, Krystyna
AU  - Ossowska K
AD  - Department of Neuropsychopharmacology, Polish Academy of Sciences, Smetna St. 12, 
      31-343 Krakow, Poland.
FAU - Dencher, Norbert A
AU  - Dencher NA
AD  - Physical Biochemistry, Department of Chemistry, Technische Universitat Darmstadt, 
      Alarich-Weiss-Str. 4, D-64287 Darmstadt, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160201
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Mitochondrial Proteins)
RN  - 8HW4YBZ748 (Oxidopamine)
SB  - IM
MH  - Animals
MH  - Cell Membrane/*metabolism/pathology
MH  - Dopaminergic Neurons/*metabolism/pathology
MH  - Male
MH  - Mitochondria/*metabolism/pathology
MH  - Mitochondrial Proteins/metabolism
MH  - Oxidative Phosphorylation/*drug effects
MH  - Oxidopamine/*adverse effects/pharmacology
MH  - Parkinson Disease, Secondary/*metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Compensatory processes
OT  - Mitochondrial membrane viscosity
OT  - Neurodegeneration
OT  - OxPhos supercomplex assembly
OT  - Parkinson's disease
EDAT- 2016/02/05 06:00
MHDA- 2019/03/29 06:00
CRDT- 2016/02/05 06:00
PHST- 2015/10/22 00:00 [received]
PHST- 2016/01/27 00:00 [revised]
PHST- 2016/01/29 00:00 [accepted]
PHST- 2016/02/05 06:00 [entrez]
PHST- 2016/02/05 06:00 [pubmed]
PHST- 2019/03/29 06:00 [medline]
AID - S0925-4439(16)30025-4 [pii]
AID - 10.1016/j.bbadis.2016.01.022 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2016 Apr;1862(4):741-753. doi: 
      10.1016/j.bbadis.2016.01.022. Epub 2016 Feb 1.