Connecting variability in global transcription rate to mitochondrial variability.

Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular rates of transcription. We also found marked c...

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Main Authors: Ricardo Pires das Neves, Nick S Jones, Lorena Andreu, Rajeev Gupta, Tariq Enver, Francisco J Iborra
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-12-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000560&type=printable
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author Ricardo Pires das Neves
Nick S Jones
Lorena Andreu
Rajeev Gupta
Tariq Enver
Francisco J Iborra
author_facet Ricardo Pires das Neves
Nick S Jones
Lorena Andreu
Rajeev Gupta
Tariq Enver
Francisco J Iborra
author_sort Ricardo Pires das Neves
collection DOAJ
description Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular rates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. We undertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Following this, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration of other nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels and available [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, or higher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also found evidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughter studies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria at division. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters have relatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability in transcription rate.
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spelling doaj-art-8f8a6b3d7bb942b2a6057da38c626b022025-08-20T02:32:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852010-12-01812e100056010.1371/journal.pbio.1000560Connecting variability in global transcription rate to mitochondrial variability.Ricardo Pires das NevesNick S JonesLorena AndreuRajeev GuptaTariq EnverFrancisco J IborraPopulations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular rates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. We undertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Following this, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration of other nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels and available [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, or higher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also found evidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughter studies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria at division. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters have relatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability in transcription rate.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000560&type=printable
spellingShingle Ricardo Pires das Neves
Nick S Jones
Lorena Andreu
Rajeev Gupta
Tariq Enver
Francisco J Iborra
Connecting variability in global transcription rate to mitochondrial variability.
PLoS Biology
title Connecting variability in global transcription rate to mitochondrial variability.
title_full Connecting variability in global transcription rate to mitochondrial variability.
title_fullStr Connecting variability in global transcription rate to mitochondrial variability.
title_full_unstemmed Connecting variability in global transcription rate to mitochondrial variability.
title_short Connecting variability in global transcription rate to mitochondrial variability.
title_sort connecting variability in global transcription rate to mitochondrial variability
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000560&type=printable
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