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  The TFAM-to-mtDNA ratio defines inner-cellular nucleoid populations with distinct activity levels

Brüser, C., Keller-Findeisen, J., & Jakobs, S. (2021). The TFAM-to-mtDNA ratio defines inner-cellular nucleoid populations with distinct activity levels. Cell Reports, 37(8): 110000. doi:10.1016/j.celrep.2021.110000.

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 Creators:
Brüser, C.1, Author              
Keller-Findeisen, J.2, Author              
Jakobs, S.1, Author              
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1Research Group of Mitochondrial Structure and Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_578566              
2Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

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Free keywords: DNA packaging; STED nanoscopy; mitochondrial gene expression; mtDNA mutations; mtDNA replication
 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.

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Language(s): eng - English
 Dates: 2021-11-232021-11-23
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.celrep.2021.110000
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Title: Cell Reports
Source Genre: Journal
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Pages: 9 Volume / Issue: 37 (8) Sequence Number: 110000 Start / End Page: - Identifier: -