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

Hanock Elkon, Jermy Don, Eldad Melamed, Ilan Ziv, Anat Shirvan, Daniel Offen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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 autosomaldominant 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 mithochondrial 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.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalJournal of Molecular Neuroscience
Volume18
Issue number3
DOIs
StatePublished - 2002

Funding

FundersFunder number
National Parkinson Foundation

    Keywords

    • Coimmunoprecipitation
    • Cytochrome c oxidase
    • In vitro translation
    • Parkinson's disease
    • Potassium cyanide
    • Two-hybrid system
    • α-synuclein

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