Mitochondrial variability as a source of extrinsic cellular noise.

We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription, translation, stem cell differentiation and response to medication, but...

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Autores principales:	Iain G Johnston, Bernadett Gaal, Ricardo Pires das Neves, Tariq Enver, Francisco J Iborra, Nick S Jones
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/82408ccaf4d2433c9af0c10e33ca99ff
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spelling	oai:doaj.org-article:82408ccaf4d2433c9af0c10e33ca99ff2021-11-18T05:51:31ZMitochondrial variability as a source of extrinsic cellular noise.1553-734X1553-735810.1371/journal.pcbi.1002416https://doaj.org/article/82408ccaf4d2433c9af0c10e33ca99ff2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412363/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription, translation, stem cell differentiation and response to medication, but the specific random influences that affect these processes have yet to be clearly elucidated. Here we present a mechanism by which variability in mitochondrial volume and functionality, along with cell cycle dynamics, is linked to variability in transcription rate and hence has a profound effect on downstream cellular processes. Our model mechanism is supported by an appreciable volume of recent experimental evidence, and we present the results of several new experiments with which our model is also consistent. We find that noise due to mitochondrial variability can sometimes dominate over other extrinsic noise sources (such as cell cycle asynchronicity) and can significantly affect large-scale observable properties such as cell cycle length and gene expression levels. We also explore two recent regulatory network-based models for stem cell differentiation, and find that extrinsic noise in transcription rate causes appreciable variability in the behaviour of these model systems. These results suggest that mitochondrial and transcriptional variability may be an important mechanism influencing a large variety of cellular processes and properties.Iain G JohnstonBernadett GaalRicardo Pires das NevesTariq EnverFrancisco J IborraNick S JonesPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 3, p e1002416 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Iain G Johnston Bernadett Gaal Ricardo Pires das Neves Tariq Enver Francisco J Iborra Nick S Jones Mitochondrial variability as a source of extrinsic cellular noise.
description	We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription, translation, stem cell differentiation and response to medication, but the specific random influences that affect these processes have yet to be clearly elucidated. Here we present a mechanism by which variability in mitochondrial volume and functionality, along with cell cycle dynamics, is linked to variability in transcription rate and hence has a profound effect on downstream cellular processes. Our model mechanism is supported by an appreciable volume of recent experimental evidence, and we present the results of several new experiments with which our model is also consistent. We find that noise due to mitochondrial variability can sometimes dominate over other extrinsic noise sources (such as cell cycle asynchronicity) and can significantly affect large-scale observable properties such as cell cycle length and gene expression levels. We also explore two recent regulatory network-based models for stem cell differentiation, and find that extrinsic noise in transcription rate causes appreciable variability in the behaviour of these model systems. These results suggest that mitochondrial and transcriptional variability may be an important mechanism influencing a large variety of cellular processes and properties.
format	article
author	Iain G Johnston Bernadett Gaal Ricardo Pires das Neves Tariq Enver Francisco J Iborra Nick S Jones
author_facet	Iain G Johnston Bernadett Gaal Ricardo Pires das Neves Tariq Enver Francisco J Iborra Nick S Jones
author_sort	Iain G Johnston
title	Mitochondrial variability as a source of extrinsic cellular noise.
title_short	Mitochondrial variability as a source of extrinsic cellular noise.
title_full	Mitochondrial variability as a source of extrinsic cellular noise.
title_fullStr	Mitochondrial variability as a source of extrinsic cellular noise.
title_full_unstemmed	Mitochondrial variability as a source of extrinsic cellular noise.
title_sort	mitochondrial variability as a source of extrinsic cellular noise.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/82408ccaf4d2433c9af0c10e33ca99ff
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Mitochondrial variability as a source of extrinsic cellular noise.

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