Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles.
Alpha-synuclein, a presynaptic protein associated with Parkinson's disease, is found as both soluble cytosolic and membrane-bound forms. Although the function of alpha-synuclein is unknown, several observations suggest that its association with membranes is important. In the present study we investigated the effect of alpha-synuclein on lipid oxidation in membranes containing phospholipids with unsaturated fatty acids. The kinetics of lipid oxidation were monitored by the change in fluorescence intensity of the dye C11-BODIPY. We find that monomeric alpha-synuclein efficiently prevented lipid oxidation, whereas fibrillar alpha-synuclein had no such effect. Our data suggest that the prevention of unsaturated lipid oxidation by alpha-synuclein requires that it bind to the lipid membrane. The antioxidant function of alpha-synuclein is attributed to its facile oxidation via the formation of methionine sulfoxide, as shown by mass spectrometry. These findings suggest that the inhibition of lipid oxidation by alpha-synuclein may be a physiological function of the protein.
Zhu
Min
M
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Qin
Zhi-Jie
ZJ
Hu
Dongmei
D
Munishkina
Larissa A
LA
Fink
Anthony L
AL
D000975:Antioxidants / Q000378:metabolism*; D001896:Boron Compounds; D002942:Circular Dichroism; D005453:Fluorescence; D007700:Kinetics; D008081:Liposomes; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D051844:alpha-Synuclein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000975:Antioxidants; D001896:Boron Compounds; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D051844:alpha-Synuclein; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine