alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity.
alpha-Synuclein (alpha-Syn) abnormality and mitochondrial deficiency are two major changes in the brain of patients with Parkinson's disease (PD). A link between alpha-Syn and mitochondria in PD has been demonstrated by a recent study showing that accumulation of alpha-Syn in the mitochondria from the PD-vulnerable brain regions was associated with decreased complex I activity of these mitochondria. In this study, we examined the normal expressions of alpha-Syn in mitochondria from different regions of the rat brain. We showed that alpha-Syn was highly expressed in the mitochondria in olfactory bulb, hippocampus, striatum, and thalamus, where the cytosolic alpha-Syn was also rich. However, the cerebral cortex and cerebellum were two exceptions, which contained rich cytosolic alpha-Syn but very low or even undetectable levels of mitochondrial alpha-Syn. The close quantitative association between mitochondrial and cytosolic alpha-Syn in most brain regions, suggests that the concentration of cytosolic alpha-Syn may determine the amount of alpha-Syn in mitochondria. This is partially supported by the in vitro experiment showing that incubation of alpha-Syn with endogenous alpha-Syn-undetectable cerebellar mitochondria caused a dose-dependent transport of alpha-Syn to the mitochondria. Moreover, we found that the inhibitory effect of alpha-Syn on complex I activity of mitochondrial respiratory chain was also dose-dependent. These results suggest that alpha-Syn in mitochondria is differentially expressed in different brain regions and the background levels of mitochondrial alpha-Syn may be a potential factor affecting mitochondrial function and predisposing some neurons to degeneration.
Department of Neurobiology and Sino-Japan Joint Laboratory for Neurodegenerative Diseases, Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Xuanwu Hospital of China Capital Medical University, Beijing, China.
Guangwei
G
Liu
Chunyan
C
Zhang
Juanjuan
J
Yin
Xin
X
Li
Furong
F
Cheng
Yaohua
Y
Li
Hui
H
Yang
Kenji
K
Uéda
Piu
P
Chan
Shun
S
Yu
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D042967:Electron Transport Complex I / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D051844:alpha-Synuclein / Q000096:biosynthesis*
D051844:alpha-Synuclein; D042967:Electron Transport Complex I