Glutaredoxin is essential for maintenance of brain mitochondrial complex I: studies with MPTP.

Rajappa S. Kenchappa, Vijayalakshmi Ravindranath

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Mitochondrial complex I dysfunction is implicated in the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Identification of factors involved in maintenance and restoration of complex I function could potentially help to develop prophylactic and therapeutic strategies for treatment of this class of disorders. Down-regulation of glutaredoxin (thioltransferase, a thiol disulfide oxido-reductase) using antisense oligonucleotides results in the loss of mitochondrial complex I activity in mouse brain. 1-Methyl-4-phenyl-1,2,3,6,tetrahydro-pyridine (MPTP), the neurotoxin that causes Parkinson's disease-like symptoms in primates and dopaminergic cell loss in mice, acts through the inhibition of complex I. Regeneration of complex I activity in the striatum occurs concurrently with increase in glutaredoxin activity, 4 h after the neurotoxic insult, and is mediated through activation of activating protein-1. Down-regulation of glutaredoxin using anti-sense oligonucleotides prevents recovery of complex I in the striatum after MPTP treatment, providing support for the critical role for glutaredoxin in recovery of mitochondrial function in brain. Maintenance and restoration of protein thiol homeostasis by glutaredoxin may be important factors in preventing complex I dysfunction.

Original languageEnglish (US)
Pages (from-to)717-719
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number6
DOIs
StatePublished - Apr 2003

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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