期刊
EXPERIMENTAL CELL RESEARCH
卷 314, 期 10, 页码 2076-2089出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.03.012
关键词
alpha-synuclein; mitochondria; pH; Parkinson's disease; oxidative stress; metabolic dysfunction
资金
- Intramural NIH HHS [Z99 HL999999] Funding Source: Medline
Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson's disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein alpha-synuclein or its familial mutants often sensitizes neurons to oxidative stress and to damage by mitochondrial toxins. This effect is thought to be indirect, since little evidence physically linking alpha-synuclein to mitochondria has been reported. Here, we show that the distribution of a-synuclein within neuronal and non-neuronal cells is dependent on intracellular pH. Cytosolic acidification induces translocation of a-synuclein from the cytosol onto the surface of mitochondria. Translocation occurs rapidly under artificially-induced low pH conditions and as a result of pH changes during oxidative or metabolic stress. Binding is likely facilitated by low pH-induced exposure of the mitochondria-specific lipid cardiolipin. These results imply a direct role for alpha-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link alpha-synuclein to other PD genes in regulating mitochondrial homeostasis. Published by Elsevier Inc.
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