C17orf80 binds the mitochondrial genome to promote its replication.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 10 2023
02 10 2023
Historique:
received:
09
02
2023
revised:
26
06
2023
accepted:
17
07
2023
pmc-release:
07
03
2024
medline:
8
9
2023
pubmed:
7
9
2023
entrez:
7
9
2023
Statut:
ppublish
Résumé
Serving as the power plant and signaling hub of a cell, mitochondria contain their own genome which encodes proteins essential for energy metabolism and forms DNA-protein assemblies called nucleoids. Mitochondrial DNA (mtDNA) exists in multiple copies within each cell ranging from hundreds to tens of thousands. Maintaining mtDNA homeostasis is vital for healthy cells, and its dysregulation causes multiple human diseases. However, the players involved in regulating mtDNA maintenance are largely unknown though the core components of its replication machinery have been characterized. Here, we identify C17orf80, a functionally uncharacterized protein, as a critical player in maintaining mtDNA homeostasis. C17orf80 primarily localizes to mitochondrial nucleoid foci and exhibits robust double-stranded DNA binding activity throughout the mitochondrial genome, thus constituting a bona fide new mitochondrial nucleoid protein. It controls mtDNA levels by promoting mtDNA replication and plays important roles in mitochondrial metabolism and cell proliferation. Our findings provide a potential target for therapeutics of human diseases associated with defective mtDNA control.
Identifiants
pubmed: 37676315
pii: 276241
doi: 10.1083/jcb.202302037
pmc: PMC10484793
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Mitochondrial Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Wu et al.
Références
Hum Mol Genet. 2011 Apr 15;20(8):1653-9
pubmed: 21296868
Mol Genet Metab. 2022 Sep-Oct;137(1-2):40-48
pubmed: 35914366
Nucleic Acids Res. 2003 Mar 15;31(6):1640-5
pubmed: 12626705
J Biol Chem. 2006 Sep 1;281(35):25791-802
pubmed: 16825194
J Physiol. 2003 Oct 15;552(Pt 2):335-44
pubmed: 14561818
Hum Mol Genet. 2010 Jul 1;19(13):2695-705
pubmed: 20413656
Cell Metab. 2020 Sep 1;32(3):479-497.e9
pubmed: 32877691
Nat Cell Biol. 2022 Feb;24(2):181-193
pubmed: 35165413
Nucleic Acids Res. 2002 May 1;30(9):2004-10
pubmed: 11972339
Nature. 2016 Apr 7;532(7597):112-6
pubmed: 27027295
Mol Biol Cell. 2003 Apr;14(4):1583-96
pubmed: 12686611
Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):914-20
pubmed: 22142616
Hum Mutat. 2008 Sep;29(9):E150-72
pubmed: 18546365
Nat Genet. 2006 May;38(5):515-7
pubmed: 16604074
Nature. 2014 Jan 16;505(7483):335-43
pubmed: 24429632
Carcinogenesis. 2004 Jun;25(6):1005-10
pubmed: 14764459
Biochim Biophys Acta. 2012 May;1820(5):553-64
pubmed: 21871538
Int J Biochem Cell Biol. 2009 Oct;41(10):1899-906
pubmed: 19703654
Mol Cell Biochem. 2015 Nov;409(1-2):283-305
pubmed: 26286847
Nature. 1981 Apr 9;290(5806):457-65
pubmed: 7219534
Circ Res. 2001 Mar 16;88(5):529-35
pubmed: 11249877
Curr Opin Genet Dev. 2016 Jun;38:52-62
pubmed: 27065468
J Inherit Metab Dis. 2017 Jul;40(4):587-599
pubmed: 28324239
Biochimie. 2014 May;100:219-26
pubmed: 24076128
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10726-31
pubmed: 15247418
J Biol Chem. 2005 Aug 5;280(31):28785-91
pubmed: 15946949
J Clin Invest. 2003 Jun;111(12):1913-21
pubmed: 12813027
Cell Metab. 2021 Dec 7;33(12):2464-2483.e18
pubmed: 34800366
Nat Rev Mol Cell Biol. 2012 Oct;13(10):659-71
pubmed: 22992591
Nat Genet. 2001 Jul;28(3):223-31
pubmed: 11431692
Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):921-9
pubmed: 22465614
J Neurochem. 2005 May;93(4):953-62
pubmed: 15857398
J Cell Sci. 2004 Jun 1;117(Pt 13):2653-62
pubmed: 15138283
J Cancer Res Clin Oncol. 2009 Aug;135(8):983-9
pubmed: 19125299
Annu Rev Biochem. 2007;76:679-99
pubmed: 17408359
Crit Rev Biochem Mol Biol. 2012 Jan-Feb;47(1):64-74
pubmed: 22176657
Physiol Rev. 2014 Jul;94(3):909-50
pubmed: 24987008
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1539-1555
pubmed: 28215579
Cell Mol Life Sci. 2011 Jan;68(2):219-33
pubmed: 20927567
Mol Biol Cell. 2007 Sep;18(9):3225-36
pubmed: 17581862
Biochem J. 2009 Jan 1;417(1):1-13
pubmed: 19061483
Biochim Biophys Acta. 2010 Aug;1797(8):1378-88
pubmed: 20417176
Neurology. 1997 May;48(5):1244-53
pubmed: 9153451
Circ Res. 2010 May 14;106(9):1541-8
pubmed: 20339121
Hum Mol Genet. 2007 Jun 15;16(12):1400-11
pubmed: 17483096
Diabetes. 2004 Feb;53 Suppl 1:S103-9
pubmed: 14749274
J Biol Chem. 2008 Feb 8;283(6):3665-3675
pubmed: 18063578
Annu Rev Biochem. 2016 Jun 2;85:133-60
pubmed: 27023847
J Med Genet. 2011 Oct;48(10):669-81
pubmed: 21880868
Nat Protoc. 2021 May;16(5):2698-2721
pubmed: 33911256
Exp Cell Res. 2003 Sep 10;289(1):133-42
pubmed: 12941611
Nat Genet. 1999 Oct;23(2):147
pubmed: 10508508
Mol Neurodegener. 2010 May 26;5:21
pubmed: 20504367
Am J Hum Genet. 1991 Mar;48(3):492-501
pubmed: 1998336