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FMRpolyG alters mitochondrial transcripts level and respiratory chain complex assembly in Fragile X associated tremor/ataxia syndrome [FXTAS].

Authors :
Gohel D
Sripada L
Prajapati P
Singh K
Roy M
Kotadia D
Tassone F
Charlet-Berguerand N
Singh R
Source :
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2019 Jun 01; Vol. 1865 (6), pp. 1379-1388. Date of Electronic Publication: 2019 Feb 13.
Publication Year :
2019

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by an expansion of 55 to 200 CGG repeats (premutation) in FMR1. These CGG repeats are Repeat Associated non-ATG (RAN) translated into a small and pathogenic protein, FMRpolyG. The cellular and molecular mechanisms of FMRpolyG toxicity are unclear. Various mitochondrial dysfunctions have been observed in FXTAS patients and animal models. However, the causes of these mitochondrial alterations are not well understood. In the current study, we investigated interaction of FMRpolyG with mitochondria and its role in modulating mitochondrial functions. Beside nuclear inclusions, FMRpolyG also formed small cytosolic aggregates that interact with mitochondria both in cell and mouse model of FXTAS. Importantly, expression of FMRpolyG reduces ATP levels, mitochondrial transmembrane potential, mitochondrial supercomplexes assemblies and activities and expression of mitochondrial DNA encoded transcripts in cell and animal model of FXTAS, as well as in FXTAS patient brain tissues. Overall, these results suggest that FMRpolyG alters mitochondrial functions, bioenergetics and initiates cell death. The further study in this direction will help to establish the role of mitochondria in FXTAS conditions.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-260X
Volume :
1865
Issue :
6
Database :
MEDLINE
Journal :
Biochimica et biophysica acta. Molecular basis of disease
Publication Type :
Academic Journal
Accession number :
30771487
Full Text :
https://doi.org/10.1016/j.bbadis.2019.02.010