Mitochondrial function in skeletal myofibers is controlled by a TRF2-SIRT3 axis over lifetime.
Adolescent
Adult
Aged
Aging
/ metabolism
Animals
Cells, Cultured
Down-Regulation
/ genetics
Female
Gene Knockdown Techniques
Humans
Male
Mice
Mice, Knockout
Middle Aged
Mitochondria
/ metabolism
Muscle Fibers, Skeletal
/ metabolism
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ genetics
Sirtuin 3
/ metabolism
Telomere
/ metabolism
Telomere Shortening
/ genetics
Telomeric Repeat Binding Protein 2
/ genetics
Young Adult
aging
mitochondria
postmitotic cells
skeletal muscle
telomeres
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
14
08
2019
revised:
23
11
2019
accepted:
10
12
2019
pubmed:
29
1
2020
medline:
11
5
2021
entrez:
29
1
2020
Statut:
ppublish
Résumé
Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere-capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2-compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2-compromised human myotubes. Altogether, these results reveal a TRF2-SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism.
Identifiants
pubmed: 31991048
doi: 10.1111/acel.13097
pmc: PMC7059141
doi:
Substances chimiques
Reactive Oxygen Species
0
Sirt3 protein, mouse
0
TERF2 protein, human
0
TRF2 protein, mouse
0
Telomeric Repeat Binding Protein 2
0
SIRT3 protein, human
EC 3.5.1.-
Sirtuin 3
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13097Informations de copyright
© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Références
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13120-13125
pubmed: 27799523
Nucleic Acids Res. 2005 Feb 24;33(4):1230-9
pubmed: 15731343
Development. 2011 Sep;138(17):3625-37
pubmed: 21828091
Front Aging Neurosci. 2013 Sep 06;5:48
pubmed: 24046746
Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9276-9281
pubmed: 30150400
Nature. 2016 Feb 11;530(7589):184-9
pubmed: 26840489
Aging Cell. 2020 Mar;19(3):e13097
pubmed: 31991048
Genes Dev. 2014 Nov 15;28(22):2464-76
pubmed: 25403178
Cell Rep. 2018 Sep 4;24(10):2589-2595
pubmed: 30184494
PLoS One. 2011;6(6):e21347
pubmed: 21731710
Nat Med. 2015 Jan;21(1):76-80
pubmed: 25501907
EMBO Rep. 2013 Apr;14(4):356-63
pubmed: 23429341
Anat Rec. 1971 Aug;170(4):421-35
pubmed: 5118594
Ann Rehabil Med. 2015 Apr;39(2):155-62
pubmed: 25932410
Ciba Found Symp. 1997;211:129-39; discussion 139-44
pubmed: 9524755
Anat Rec. 1974 Dec;180(4):589-95
pubmed: 4440878
Nature. 2009 Jul 30;460(7255):627-31
pubmed: 19554048
Cell Metab. 2013 Aug 6;18(2):239-50
pubmed: 23931755
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Cell. 2011 Sep 2;146(5):682-95
pubmed: 21884931
Aging Cell. 2017 Feb;16(1):4-16
pubmed: 27686535
Cell Res. 2011 Jul;21(7):1028-38
pubmed: 21423270
EMBO Rep. 2002 Nov;3(11):1055-61
pubmed: 12393752
Genes Dev. 2008 Mar 1;22(5):654-67
pubmed: 18283121
J Physiol. 2016 Sep 15;594(18):5081-92
pubmed: 26893258
Muscle Nerve. 2014 Nov;50(5):723-32
pubmed: 25186345
PLoS Biol. 2016 Dec 15;14(12):e2000016
pubmed: 27977688
Nature. 2011 Feb 17;470(7334):359-65
pubmed: 21307849
Aging (Albany NY). 2017 Apr;9(4):1219-1232
pubmed: 28437249
Nat Cell Biol. 2013 Jul;15(7):818-28
pubmed: 23792691
Curr Opin Clin Nutr Metab Care. 2017 May;20(3):186-190
pubmed: 28376051
PLoS Genet. 2016 Jan 20;12(1):e1005798
pubmed: 26789415
PLoS Biol. 2007 May;5(5):e110
pubmed: 17472436
Cell Rep. 2013 Jun 27;3(6):2059-74
pubmed: 23791526
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2700-5
pubmed: 19196970
Nature. 2014 May 22;509(7501):439-46
pubmed: 24848057
Age (Dordr). 2014 Feb;36(1):469-78
pubmed: 23839864
Genome Biol. 2015 Sep 23;16:206
pubmed: 26399229
J Exp Zool. 1978 Dec;206(3):451-6
pubmed: 712350
Cell Rep. 2016 Dec 20;17(12):3107-3114
pubmed: 28009281
Handb Clin Neurol. 2013;113:1299-310
pubmed: 23622355
Trends Biochem Sci. 2002 Jul;27(7):339-44
pubmed: 12114022
Nat Commun. 2015 Apr 10;6:6670
pubmed: 25858807
Cell Res. 2011 Jul;21(7):1013-27
pubmed: 21423278
Nat Commun. 2014 Nov 17;5:5467
pubmed: 25399868
Mol Cell. 2012 Sep 28;47(6):839-50
pubmed: 22885005
Aging Cell. 2002 Dec;1(2):132-9
pubmed: 12882343
Cell Discov. 2017 Sep 26;3:17034
pubmed: 28955502
Cell. 2004 Apr 30;117(3):399-412
pubmed: 15109499
Nat Cell Biol. 2014 Dec;16(12):1168-1179
pubmed: 25419847
Cell Rep. 2017 Jun 13;19(11):2396-2409
pubmed: 28614723
J Gerontol A Biol Sci Med Sci. 1995 Nov;50 Spec No:11-6
pubmed: 7493202
Nat Commun. 2013;4:1597
pubmed: 23511462
Cell Death Differ. 2012 Jun;19(6):968-79
pubmed: 22139133
Nat Struct Mol Biol. 2016 Dec;23(12):1092-1100
pubmed: 27820808
Lancet. 1989 Mar 25;1(8639):642-5
pubmed: 2564461
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52
pubmed: 18794531
Genome Res. 2015 Dec;25(12):1781-90
pubmed: 26359233
J Cell Sci. 2008 Apr 1;121(Pt 7):1046-53
pubmed: 18334557
Am J Hum Genet. 2006 Sep;79(3):469-80
pubmed: 16909385
Genes Dev. 2018 May 1;32(9-10):658-669
pubmed: 29773556
Cell Metab. 2016 Feb 9;23(2):303-14
pubmed: 26686024
Biochim Biophys Acta. 2014 Apr;1840(4):1254-65
pubmed: 24211250
J Vis Exp. 2015 Jan 18;(95):52307
pubmed: 25651101
Development. 2012 Aug;139(16):2845-56
pubmed: 22833472
Stem Cell Res. 2014 Nov;13(3 Pt A):492-507
pubmed: 25262445
Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E151-7
pubmed: 16926381
Nat Rev Genet. 2014 Jul;15(7):491-503
pubmed: 24913665
J Anat. 1987 Aug;153:31-45
pubmed: 3429325
Nat Rev Mol Cell Biol. 2007 Oct;8(10):825-38
pubmed: 17885666
J Mol Cell Cardiol. 2012 Mar;52(3):520-5
pubmed: 22119802
Mol Cell Biol. 2003 Mar;23(5):1498-508
pubmed: 12588971
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5378-83
pubmed: 12702777