Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells

Gustavo Della-Flora Nunes, Emma R. Wilson, Leandro N. Marziali, Edward Hurley, Nicholas Silvestri, Bin He, Bert W. O’Malley, Bogdan Beirowski, Yannick Poitelon, Lawrence Wrabetz, M. Laura Feltri

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


In peripheral nerves, Schwann cells form myelin and provide trophic support to axons. We previously showed that the mitochondrial protein prohibitin 2 can localize to the axon-Schwann-cell interface and is required for developmental myelination. Whether the homologous protein prohibitin 1 has a similar role, and whether prohibitins also play important roles in Schwann cell mitochondria is unknown. Here, we show that deletion of prohibitin 1 in Schwann cells minimally perturbs development, but later triggers a severe demyelinating peripheral neuropathy. Moreover, mitochondria are heavily affected by ablation of prohibitin 1 and demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, in response to mitochondrial damage, Schwann cells trigger the integrated stress response, but, contrary to what was previously suggested, this response is not detrimental in this context. These results identify a role for prohibitin 1 in myelin integrity and advance our understanding about the Schwann cell response to mitochondrial damage.

Original languageEnglish (US)
Article number3285
JournalNature Communications
Issue number1
StatePublished - Jun 2 2021


  • Animals
  • Aspartate-Ammonia Ligase/genetics
  • Axons/metabolism
  • Eukaryotic Initiation Factor-2/genetics
  • Female
  • Femoral Nerve/metabolism
  • Heat-Shock Proteins/genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondria/metabolism
  • Myelin Sheath/metabolism
  • Phosphoenolpyruvate Carboxykinase (ATP)/genetics
  • Protein Isoforms/genetics
  • RNA, Messenger/genetics
  • Repressor Proteins/deficiency
  • Schwann Cells/metabolism
  • Sciatic Nerve/metabolism
  • Stress, Physiological
  • Tibial Nerve/metabolism
  • Transcription Factor CHOP/genetics
  • X-Box Binding Protein 1/genetics
  • gamma-Glutamylcyclotransferase/genetics

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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