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

Autor: Lawrence Wrabetz, Bin He, Bogdan Beirowski, Gustavo Della-Flora Nunes, Leandro N. Marziali, Emma R. Wilson, Bert W. O'Malley, Yannick Poitelon, M. Laura Feltri, Edward Hurley, Nicholas Silvestri
Rok vydání: 2021
Předmět:
Male
X-Box Binding Protein 1
0301 basic medicine
Myelin biology and repair
Eukaryotic Initiation Factor-2
General Physics and Astronomy
Mitochondrion
Mice
Myelin
0302 clinical medicine
Protein Isoforms
Prohibitin
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Myelin Sheath
Multidisciplinary
Aspartate-Ammonia Ligase
Sciatic Nerve
Schwann cell
Mitochondria
Cell biology
medicine.anatomical_structure
Female
Femoral Nerve
Science
Transgene
Mice
Transgenic
Context (language use)
Biology
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Stress
Physiological
Prohibitins
medicine
Animals
Integrated stress response
RNA
Messenger
General Chemistry
medicine.disease
Axons
Mice
Inbred C57BL
Repressor Proteins
030104 developmental biology
Peripheral neuropathy
nervous system
Schwann Cells
Tibial Nerve
Phosphoenolpyruvate Carboxykinase (ATP)
Transcription Factor CHOP
gamma-Glutamylcyclotransferase
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-021-23552-8
Popis: 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.
Prohibitin 2 can localize to the axon-Schwann-cell interface and is required for myelin formation. Here, the authors show that deletion of prohibitin 1 in Schwann cells instead triggers severe myelin loss likely caused by mitochondrial dysfunction, and not rescued by inhibition of the ensuing integrated stress response.
Databáze: OpenAIRE
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