Activation of mTORC1 and c-Jun by Prohibitin1 loss in Schwann cells may link mitochondrial dysfunction to demyelination.
O'Malley, Bert W
eLife Sciences Publications, Ltd
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Della-Flora Nunes, G., Wilson, E. R., Hurley, E., He, B., O'Malley, B. W., Poitelon, Y., Wrabetz, L., & et al. (2021). Activation of mTORC1 and c-Jun by Prohibitin1 loss in Schwann cells may link mitochondrial dysfunction to demyelination.. Elife, 10 e66278. https://doi.org/10.7554/eLife.66278
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 in mice, but the mechanism that causes failure of myelin maintenance remained unknown. Here, we report that mTORC1 and c-Jun are continuously activated in the absence of Phb1, likely as part of the SC response 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 c-Jun may play a critical role as executioners of demyelination in the context of perturbations to SC mitochondria.
PHB1, demyelination, mechanistic target of rapamycin, mitochondrial stress response, mouse, myelin maintenance, neuroscience, schwann cells, Animals, Demyelinating Diseases, Mechanistic Target of Rapamycin Complex 1, Mice, Mice, Knockout, Mitochondria, Myelin Sheath, Prohibitins, Proto-Oncogene Proteins c-jun, Repressor Proteins, Schwann Cells, Up-Regulation
External DOI: https://doi.org/10.7554/eLife.66278
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332107
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
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