SUMMARY:
mTORC2 is a novel molecular target that lies upstream of AKT to restore the cell proliferation rate in CMT2A fibroblasts.
TITLE:
Torin1 restores proliferation rate in Charcot-Marie-Tooth disease type 2A cells harbouring MFN2 (mitofusin 2) mutation
DESCRIPTION:
CONCLUSIONS: Overall, our study provides evidence for mTORC2, as a novel molecular target that lies upstream of AKT to restore the cell proliferation rate in CMT2A fibroblasts.
CONTENT:
Acta Myol. 2022 Dec 31;41(4):201-206. doi: 10.36185/2532-1900-085. eCollection 2022.
ABSTRACT
OBJECTIVE: Mitofusin 2 (MFN2) is a mitochondrial outer membrane protein that serves primarily as a mitochondrial fusion protein but has additional functions including the tethering of mitochondrial-endoplasmic reticulum membranes, movement of mitochondria along axons, and control of the quality of mitochondria. Intriguingly, MFN2 has been referred to play a role in regulating cell proliferation in several cell types such that it acts as a tumour suppressor role in some forms of cancer. Previously, we found that fibroblasts derived from a Charcot-Marie-Tooth disease type 2A (CMT2A) patient with a mutation in the GTPase domain of MFN2 exhibit increased proliferation and decreased autophagy.
METHODS: Primary fibroblasts from a young patient affected by CMT2A harbouring c.650G > T/p.Cys217Phe mutation in the MFN2 gene were evaluated versus a healthy control to measure the proliferation rate by growth curves analysis and to assess the phosphorylation of protein kinase B (AKT) at Ser473 in response to different doses of torin1, a selective catalytic ATP-competitive mammalian target of rapamycin complex (mTOR) inhibitor, by immunoblot analysis.
RESULTS: Herein, we demonstrated that the mammalian target of rapamycin complex 2 (mTORC2) is highly activated in the CMT2AMFN2 fibroblasts to promote cell growth via the AKT(Ser473) phosphorylation-mediated signalling. We report that torin1 restores CMT2AMFN2 fibroblasts’ growth rate in a dose-dependent manner by decreasing AKT(Ser473) phosphorylation.
CONCLUSIONS: Overall, our study provides evidence for mTORC2, as a novel molecular target that lies upstream of AKT to restore the cell proliferation rate in CMT2A fibroblasts.
PMID:36793649 | PMC:PMC9896598 | DOI:10.36185/2532-1900-085
SOURCE:
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
TAGS:
mTORC2
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2023-02-03T11:21:47Z
DATE – DOI: 2023-02-03T11:21:47Z
DATE – PUBMED: 2022 Dec 31
DATE OUTPUT MATCHED: True
DATE – ADDED:
Thu, 16 Feb 2023 06:00:00 -0500
DATE – RETRIEVED:
02/16/23 07:07AM
2023-02-16T07:07:12-05:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:36793649,pmc:PMC9896598,doi:10.36185/2532-1900-085
PUBMED ID:
pubmed:36793649
DOI:
10.36185/2532-1900-085
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36793649/
LINK – DOI:
https://doi.org/10.36185/2532-1900-085
LINK – PUBLISHER:
https://www.actamyologica.it/article/torin1-restores-proliferation-rate-in-charcot-marie-tooth-disease-type-2a-cells-harbouring-mfn2-mitofusin-2-mutation/
REFERENCES:
CMT Treatment Report, Urgent Research, 2023-02-16T07:07:12-05:00, https://www.cmttreatmentreport.com.