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Updated: Nov 16, 2025
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Specific Labeling of Mitochondrial Nucleoids for Time-lapse Structured Illumination Microscopy
Published on: June 4, 2020
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Self-assembly of multi-component mitochondrial nucleoids via phase separation
Marina Feric1,2, Tyler G Demarest3, Jane Tian3
1National Cancer Institute, NIH, Bethesda, MD, USA.
The EMBO Journal
|February 23, 2021
Summary
Mitochondrial DNA (mtDNA) is organized by the TFAM protein through phase separation, forming nucleoids. Cellular stress causes these nucleoids to enlarge, revealing a conserved genome organization mechanism.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mitochondria possess an independent genome organized into nucleoids.
- Nucleoids comprise mitochondrial DNA (mtDNA) and architectural proteins like TFAM.
Purpose of the Study:
- To investigate the physical mechanisms governing mitochondrial nucleoid assembly and size control.
- To elucidate the role of TFAM in mitochondrial genome organization.
Main Methods:
- In vitro phase separation assays using TFAM and mtDNA.
- Analysis of mitochondrial nucleoid dynamics in vivo.
- Microscopy of mitochondria from healthy individuals and patients with Hutchinson-Gilford Progeria Syndrome (HGPS).
Main Results:
- TFAM protein undergoes spontaneous phase separation in vitro, forming viscoelastic droplets.
- These in vitro structures mimic the behavior of mitochondrial nucleoids (mt-nucleoids) in vivo.
- Cellular stress induces mt-nucleoid enlargement and increased transcriptional activity, observed in HGPS patient mitochondria.
Conclusions:
- Phase separation is the primary mechanism for mitochondrial nucleoid assembly and size regulation.
- TFAM-driven phase separation is crucial for organizing the mitochondrial genome.
- Mitochondrial nucleoid dynamics are responsive to cellular stress, impacting genome organization.
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