Menu
×
John L. Dart Library
Closed
Phone: (843) 722-7550
West Ashley Library
Closed
Phone: (843) 766-6635
Folly Beach Library
Closed
Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
Closed
Phone: (843) 805-6888
Village Library
Closed
Phone: (843) 884-9741
St. Paul's/Hollywood Library
Closed
Phone: (843) 889-3300
Otranto Road Library
Closed
Phone: (843) 572-4094
Mt. Pleasant Library
Closed
Phone: (843) 849-6161
McClellanville Library
Closed
Phone: (843) 887-3699
Keith Summey North Charleston Library
Closed
Phone: (843) 744-2489
John's Island Library
Closed
Phone: (843) 559-1945
Hurd/St. Andrews Library
Closed
Phone: (843) 766-2546
Miss Jane's Building (Edisto Library Temporary Location)
Closed
Phone: (843) 869-2355
Dorchester Road Library
Closed
Phone: (843) 552-6466
Baxter-Patrick James Island
Closed
Phone: (843) 795-6679
Main Library
2 p.m. – 5 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
Closed
Phone: (843) 805-6892
Mobile Library
Closed
Phone: (843) 805-6909
Today's Hours
John L. Dart Library
Closed
Phone: (843) 722-7550
West Ashley Library
Closed
Phone: (843) 766-6635
Folly Beach Library
Closed
Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
Closed
Phone: (843) 805-6888
Village Library
Closed
Phone: (843) 884-9741
St. Paul's/Hollywood Library
Closed
Phone: (843) 889-3300
Otranto Road Library
Closed
Phone: (843) 572-4094
Mt. Pleasant Library
Closed
Phone: (843) 849-6161
McClellanville Library
Closed
Phone: (843) 887-3699
Keith Summey North Charleston Library
Closed
Phone: (843) 744-2489
John's Island Library
Closed
Phone: (843) 559-1945
Hurd/St. Andrews Library
Closed
Phone: (843) 766-2546
Miss Jane's Building (Edisto Library Temporary Location)
Closed
Phone: (843) 869-2355
Dorchester Road Library
Closed
Phone: (843) 552-6466
Baxter-Patrick James Island
Closed
Phone: (843) 795-6679
Main Library
2 p.m. – 5 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
Closed
Phone: (843) 805-6892
Mobile Library
Closed
Phone: (843) 805-6909
Patron Login
menu
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Relationships between Mitochondrial Function, AMPK, and TORC1 Signaling in Lymphoblasts with Premutation Alleles of the FMR1 Gene.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Author(s): Fisher, Paul R.; Allan, Claire Y.; Sanislav, Oana; Atkinson, Anna; Ngoei, Kevin R. W.; Kemp, Bruce E.; Storey, Elsdon; Loesch, Danuta Z.; Annesley, Sarah J.
- Source:
International Journal of Molecular Sciences; Oct2021, Vol. 22 Issue 19, p10393, 1p- Subject Terms:
- Source:
- Additional Information
- Abstract: The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5' region that, in normal, healthy individuals contains 20–44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55–199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMP-activated protein kinase (AMPK) activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here, we report an enlarged and extended study of mitochondrial function and associated cellular stress-signaling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction in reactive O
2 species (ROS) levels in premutation cells and revealed for the first time that target of rapamycin complex I (TORC1) activities are reduced. Extensive correlation, multiple regression, and principal components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most "proximal" regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signaling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration, and ATP steady state levels. In addition, the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells but may presage the previously reported activation of TORC1 in FXS cells. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
Contact CCPL
Copyright 2022 Charleston County Public Library Powered By EBSCO Stacks 3.3.0 [350.3] | Staff Login
No Comments.