Journal of Molecular Neuroscience

, Volume 18, Issue 3, pp 229–238 | Cite as

Mutant and wild-type α-synuclein interact with mitochondrial cytochrome C oxidase

  • Hanock Elkon
  • Jermy Don
  • Eldad Melamed
  • Ilan Ziv
  • Anat Shirvan
  • Daniel Offen
Article

Abstract

α-synuclein, a presynaptic protein, was found to be the major component in the Lewy bodies (LB) in both inherited and sporadic Parkinson’s disease (PD). Furthermore, rare mutations of α-synuclein cause autosomal-dominant PD. However, it is unknown how α-synuclein is involved in the pathogenesis of nigral degeneration in PD. In this study, we examine the protein-protein interactions of wild-type and mutant (A53T) α-synuclein with adult human brain cDNA expression library using the yeast two-hybrid technique. We found that both normal and mutant α-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase (COX). Wild-type and mutant α-synuclein genes were further fused with c-Myc tag and translated in rabbit reticulocyte lysate. Using anti-c-Myc antibody, we demonstrated that both wild-type and mutant α-synuclein, coimmunoprecipitated with COX. We also showed that potassium cyanide, a selective COX inhibitor, synergistically enhanced the sensitivity of SH-SY5Y neuroblastoma cells to dopamine-induced cell death. In conclusion, we found specific protein-protein interactions of α-synuclein, a major LB protein, to COX, a key enzyme of the mitochondrial respiratory system. This interaction suggests that α-synuclein aggregation may contribute to enhance the mitochondrial dysfunction, which might be a key factor in the pathogenesis of PD.

Index Entries

α-synuclein coimmunoprecipitation cytochrome c oxidase in vitro translation Parkinson’s disease potassium cyanide two-hybrid system 

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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Hanock Elkon
    • 1
    • 2
  • Jermy Don
    • 3
  • Eldad Melamed
    • 1
    • 2
  • Ilan Ziv
    • 1
    • 2
  • Anat Shirvan
    • 1
    • 2
  • Daniel Offen
    • 1
    • 2
  1. 1.Felsenstein Medical Research Center, Department of Clinical Biochemistry, Sackler School of MedicineTel-Aviv UniversityIsrael
  2. 2.Department of NeurologyRabin Medical CenterPetah-TikvaIsrael
  3. 3.Faculty of Life Sciences Bar-Ilan UniversityRamat-GanIsrael

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