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Roussou, R.* ; Metzler, D.* ; Padovani, F. ; Thoma, F.* ; Schwarz, R.* ; Shraiman, B.* ; Schmoller, K.M. ; Osman, C.*

Real-time assessment of mitochondrial DNA heteroplasmy dynamics at the single-cell level.

EMBO J., DOI: 10.1038/s44318-024-00183-5 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Mitochondrial DNA (mtDNA) is present in multiple copies within cells and is required for mitochondrial ATP generation. Even within individual cells, mtDNA copies can differ in their sequence, a state known as heteroplasmy. The principles underlying dynamic changes in the degree of heteroplasmy remain incompletely understood, due to the inability to monitor this phenomenon in real time. Here, we employ mtDNA-based fluorescent markers, microfluidics, and automated cell tracking, to follow mtDNA variants in live heteroplasmic yeast populations at the single-cell level. This approach, in combination with direct mtDNA tracking and data-driven mathematical modeling reveals asymmetric partitioning of mtDNA copies during cell division, as well as limited mitochondrial fusion and fission frequencies, as critical driving forces for mtDNA variant segregation. Given that our approach also facilitates assessment of segregation between intact and mutant mtDNA, we anticipate that it will be instrumental in elucidating the mechanisms underlying the purifying selection of mtDNA.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Heteroplasmy ; Mathematical Modeling ; Mitochondria ; Mitochondrial Fission ; Mtdna; Genetic Bottleneck; Rapid Segregation; Transmission; Inheritance; Fission; Recombination; Organization; Replication; Reduction; Nucleoids
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Functional Epigenetics (IFE)
Förderungen DFG Research Grant
Human Frontier Science Program Research Grant
European Research Council
Human Frontier Science Program (HFSP)