The TFAM-to-mtDNA ratio defines inner-cellular nucleoid populations with distinct activity levels
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Details
- Authors
- Brüser, Christian ; Keller-Findeisen, Jan ; Jakobs, Stefan
- Abstract
- In human cells, generally a single mitochondrial DNA (mtDNA) is compacted into a nucleoprotein complex denoted the nucleoid. Each cell contains hundreds of nucleoids, which tend to cluster into small groups. It is unknown whether all nucleoids are equally involved in mtDNA replication and transcription or whether distinct nucleoid subpopulations exist. Here, we use multi-color STED super-resolution microscopy to determine the activity of individual nucleoids in primary human cells. We demonstrate that only a minority of all nucleoids are active. Active nucleoids are physically larger and tend to be involved in both replication and transcription. Inactivity correlates with a high ratio of the mitochondrial transcription factor A (TFAM) to the mtDNA of the individual nucleoid, suggesting that TFAM-induced nucleoid compaction regulates nucleoid replication and transcription activity in vivo. We propose that the stable population of highly compacted inactive nucleoids represents a storage pool of mtDNAs with a lower mutational load.
- Issue Date
- 2021
- Journal
- Cell Reports
- Project
- EXC 2067: Multiscale Bioimaging
TRR 274: Checkpoints of Central Nervous System Recovery - Working Group
- RG Jakobs (Structure and Dynamics of Mitochondria)
- ISSN
- 2211-1247
- Language
- English