α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease

Banerjee, Kalpita; Sinha, Maitrayee; Pham, Chi Le Lan; Jana, Sirsendu; Chanda, Dalia; Cappai, Roberto; Chakrabarti, Sasanka

doi:10.1016/j.febslet.2010.03.012

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Volume 584, Issue 8 , Pages 1571-1576, 16 April 2010

α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson’s disease

Edited by Barry Halliwell

Kalpita Banerjee
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244B, Acharya J.C. Bose Road, Kolkata 700 020, India
Maitrayee Sinha
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244B, Acharya J.C. Bose Road, Kolkata 700 020, India
Chi Le Lan Pham
- Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
Sirsendu Jana
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244B, Acharya J.C. Bose Road, Kolkata 700 020, India
Dalia Chanda
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244B, Acharya J.C. Bose Road, Kolkata 700 020, India
Roberto Cappai
- Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
Sasanka Chakrabarti
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244B, Acharya J.C. Bose Road, Kolkata 700 020, India
- Corresponding author. Address: Department of Biochemistry, Institute of Postgraduate Medical, Education and Research, UCM Building (4th Floor), 244B, Acharya J.C. Bose Road, Kolkata 700 020, India. Fax: +91 33 22234659.

Received 4 March 2010; accepted 8 March 2010. published online 10 March 2010.

Abstract

This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human α-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, α-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type α-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that α-synucleinopathy is involved in the pathogenesis of Parkinson’s disease.

Keywords: α-Synuclein, Dopamine, Parkinson’s disease, Mitochondria, Membrane potential, Phosphorylation