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Autophagy. 2017 Oct 3;13(10):1792-1794. doi: 10.1080/15548627.2017.1356552. Epub 2017 Aug 16.

Removing dysfunctional mitochondria from axons independent of mitophagy under pathophysiological conditions.

Author information

1
a Synaptic Function Section, The Porter Neuroscience Research Center , National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda , MD , USA.
2
b Department of Cell Biology and Neuroscience , Rutgers, The State University of New Jersey , Piscataway , NJ , USA.

Abstract

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.

KEYWORDS:

AD; ALS; axonal mitochondria; late endosome; mitochondrial quality control; mitochondrial transport; physiological stress; syntaphilin

PMID:
28812939
PMCID:
PMC5640196
DOI:
10.1080/15548627.2017.1356552
[Indexed for MEDLINE]
Free PMC Article

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