期刊
AUTOPHAGY
卷 13, 期 10, 页码 1792-1794出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2017.1356552
关键词
AD; ALS; axonal mitochondria; late endosome; mitochondrial quality control; mitochondrial transport; physiological stress; syntaphilin
类别
资金
- Intramural Research Program of NINDS [NIH ZIA NS003029, ZIA NS002946, NIH R01NS089737]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS002946, ZIANS003029, R01NS089737] Funding Source: NIH RePORTER
Chronic mitochondrial dysfunction has been implicated in major neurodegenerative diseases. Long-term cumulative pathological stress leads to axonal accumulation of damaged mitochondria. Therefore, the early removal of defective mitochondria from axons constitutes a critical step of mitochondrial quality control. We recently investigated the axonal mitochondrial response to mild stress in wild-type neurons and chronic mitochondrial defects in amyotrophic lateral sclerosis (ALS)- and Alzheimer disease (AD)-linked neurons. We demonstrated that remobilizing stressed mitochondria is critical for maintaining axonal mitochondrial integrity. The selective release of the mitochondrial anchoring protein SNPH (syntaphilin) from stressed mitochondria enhances their retrograde transport toward the soma before PARK2/Parkin-mediated mitophagy is activated. This SNPH-mediated response is robustly activated during the early disease stages of ALS-linked motor neurons and AD-related cortical neurons. Our study thus reveals a new mechanism for the maintenance of axonal mitochondrial integrity through SNPH-mediated coordination of mitochondrial stress and motility that is independent of mitophagy.
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