2021/02/23 by Marina Feric, Tyler G. Demarest, Jane Tian +3 · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #RNA modifications and cancer #RNA Research and Splicing #Mitochondrial Function and Pathology #Library science #Gerontology #Medicine #Computer science
paper · pdf · doi:10.15252/embj.2020107165
openalex publication_date 2021/02/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.