Removing dysfunctional mitochondria from axons independent of mitophagy under pathophysiological conditions

Mei Yao Lin, Xiu Tang Cheng, Yuxiang Xie, Qian Cai, Zu Hang Sheng

Research output: Contribution to journalComment/debatepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1792-1794
Number of pages3
Issue number10
StatePublished - Oct 3 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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

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