PT  - JOURNAL ARTICLE
AU  - Gustavo Della-Flora Nunes
AU  - Emma R. Wilson
AU  - Edward Hurley
AU  - Bin He
AU  - Bert W. O’Malley
AU  - Yannick Poitelon
AU  - Lawrence Wrabetz
AU  - M. Laura Feltri
TI  - mTORC1 and JUN are activated after deletion of Prohibitin 1 in Schwann cells and may link mitochondrial dysfunction to demyelination
AID  - 10.1101/2020.11.25.398032
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.25.398032
4099  - http://biorxiv.org/content/early/2020/11/25/2020.11.25.398032.short
4100  - http://biorxiv.org/content/early/2020/11/25/2020.11.25.398032.full
AB  - Schwann cell (SC) mitochondria are quickly emerging as an important regulator of myelin maintenance in the peripheral nervous system (PNS). However, the mechanisms underlying demyelination in the context of mitochondrial dysfunction in the PNS are incompletely understood. We recently showed that conditional ablation of the mitochondrial protein Prohibitin 1 (Phb1) in SCs causes a severe and fast progressing demyelinating peripheral neuropathy, but the mechanism that causes failure of myelin maintenance remained unknown. Here, we report that mTORC1 and JUN are continuously activated in the absence of Phb1, likely due to mitochondrial damage. Moreover, we demonstrate that these pathways are involved in the demyelination process, and that inhibition of mTORC1 using rapamycin partially rescues the demyelinating pathology. Therefore, we propose that mTORC1 and JUN may play a critical role as executioners of demyelination in the context of perturbations to SC mitochondria.Competing Interest StatementThe authors have declared no competing interest.