Alpha-synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: implications in Parkinson's disease.
This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human alpha-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, alpha-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 alpha-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 alpha-synucleinopathy is involved in the pathogenesis of Parkinson's disease.
Banerjee
Kalpita
K
Department of Biochemistry, Institute of Postgraduate Medical Education and Research, Kolkata, India. kalpitabanerjee@gmail.com
Sinha
Maitrayee
M
Pham
Chi Le Lan
Cle L
Jana
Sirsendu
S
Chanda
Dalia
D
Cappai
Roberto
R
Chakrabarti
Sasanka
S
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D051844:alpha-Synuclein / Q000235:genetics / Q000494:pharmacology*
D051844:alpha-Synuclein