Mitochondrial complex i defects increase ubiquitin in substantia nigra

Lanying Song, Gino A Cortopassi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Parkinsons disease (PD) is the second most common neurodegenerative disorder in the developed world, and is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) of midbrain. Mitochondrial complex I dysfunction has been implicated in PD pathophysiology, yet the molecular mechanism by which complex I defects may cause DA neurodegeneration remain unclear. Using Ndufs4 mouse model of mitochondrial complex I deficiency, we observed a remarkable ubiquitin protein increase in SN of Ndufs4-/- (KO) mice. By contrast, neurofilaments were significantly decreased in SN of KO mice. Furthermore, mass spectrometry and co-immunoprecipitation (Co-IP) analysis indicated an increase in ubiquitinated neurofilaments in midbrain of KO mice, whereas 20 S proteasome activities were decreased, which could potentially explain the buildup of ubiquitin protein. Collectively, these data suggest that mitochondrial complex I defects cause proteasome inhibition, a consequent increase in ubiquitinated neurofilaments and other proteins, and decrease the expression of neurofilaments that could be relevant to the mechanism of DA neuronal death in PD.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalBrain Research
Volume1594
DOIs
StatePublished - Jan 12 2015

Fingerprint

Substantia Nigra
Ubiquitin
Intermediate Filaments
Parkinson Disease
Proteasome Endopeptidase Complex
Mesencephalon
Ubiquitinated Proteins
Neurofilament Proteins
Dopaminergic Neurons
Immunoprecipitation
Neurodegenerative Diseases
Mass Spectrometry
Proteins

Keywords

  • ComplexI
  • Dopaminergic neurons
  • Neurofilaments
  • Parkinsons disease
  • Ubiquitin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Mitochondrial complex i defects increase ubiquitin in substantia nigra. / Song, Lanying; Cortopassi, Gino A.

In: Brain Research, Vol. 1594, 12.01.2015, p. 82-91.

Research output: Contribution to journalArticle

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