Self-assembly of multi-component mitochondrial nucleoids via phase separation.
TFAM
biomolecular condensate
genome organization
mitochondrial genome
phase separation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
revised:
08
01
2021
received:
27
10
2020
accepted:
19
01
2021
pubmed:
24
2
2021
medline:
21
10
2021
entrez:
23
2
2021
Statut:
ppublish
Résumé
Mitochondria contain an autonomous and spatially segregated genome. The organizational unit of their genome is the nucleoid, which consists of mitochondrial DNA (mtDNA) and associated architectural proteins. Here, we show that phase separation is the primary physical mechanism for assembly and size control of the mitochondrial nucleoid (mt-nucleoid). The major mtDNA-binding protein TFAM spontaneously phase separates in vitro via weak, multivalent interactions into droplets with slow internal dynamics. TFAM and mtDNA form heterogenous, viscoelastic structures in vitro, which recapitulate the dynamics and behavior of mt-nucleoids in vivo. Mt-nucleoids coalesce into larger droplets in response to various forms of cellular stress, as evidenced by the enlarged and transcriptionally active nucleoids in mitochondria from patients with the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS). Our results point to phase separation as an evolutionarily conserved mechanism of genome organization.
Identifiants
pubmed: 33619770
doi: 10.15252/embj.2020107165
pmc: PMC7957436
doi:
Substances chimiques
DNA, Mitochondrial
0
DNA-Binding Proteins
0
Mitochondrial Proteins
0
TFAM protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e107165Subventions
Organisme : Intramural NIH HHS
ID : Z01 AG000727
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010309
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010309
Pays : United States
Organisme : NIGMS NIH HHS
ID : FI2 GM128585
Pays : United States
Informations de copyright
© 2021 This article is a U.S. Government work and is in the public domain in the USA.
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