Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons

Nobuhiko Ohno, Hao Chiang, Don J Mahad, Grahame J Kidd, LiPing Liu, Richard M Ransohoff, Zu-Hang Sheng, Hitoshi Komuro, Bruce D Trapp

Research output: Contribution to journalArticlepeer-review


Axonal degeneration is a primary cause of permanent neurological disability in individuals with the CNS demyelinating disease multiple sclerosis. Dysfunction of axonal mitochondria and imbalanced energy demand and supply are implicated in degeneration of chronically demyelinated axons. The purpose of this study was to define the roles of mitochondrial volume and distribution in axonal degeneration following acute CNS demyelination. We show that the axonal mitochondrial volume increase following acute demyelination of WT CNS axons does not occur in demyelinated axons deficient in syntaphilin, an axonal molecule that immobilizes stationary mitochondria to microtubules. These findings were supported by time-lapse imaging of WT and syntaphilin-deficient axons in vitro. When demyelinated, axons deficient in syntaphilin degenerate at a significantly greater rate than WT axons, and this degeneration can be rescued by reducing axonal electrical activity with the Na(+) channel blocker flecainide. These results support the concept that syntaphilin-mediated immobilization of mitochondria to microtubules is required for the volume increase of axonal mitochondria following acute demyelination and protects against axonal degeneration in the CNS.

Original languageEnglish
Pages (from-to)9953-8
Number of pages6
JournalProceedings of the National Academy of Sciences
Issue number27
Publication statusPublished - 8 Jul 2014


  • Axons
  • Female
  • Humans
  • Mitochondria
  • Multiple Sclerosis
  • Myelin Sheath
  • Nerve Tissue Proteins
  • Time-Lapse Imaging
  • Vesicular Transport Proteins


Dive into the research topics of 'Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons'. Together they form a unique fingerprint.

Cite this