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Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis

Kanika Verma, Kanika Saxena, Rajashekar Donaka, Aseem Chaphalkar, Manish Kumar Rai, Anurag Shukla, Zainab Zaidi, Rohan Dandage, Dhanasekaran Shanmugam, Kausik Chakraborty
doi: https://doi.org/10.1101/540039
Kanika Verma
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: kanika.verma@igib.in
Kanika Saxena
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: knksaxena@gmail.com
Rajashekar Donaka
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: shekar.donaka@gmail.com
Aseem Chaphalkar
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: aseem.chaphalkar@gmail.com
Manish Kumar Rai
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: manish.rai@igib.in
Anurag Shukla
2 CSIR-National Chemical Laboratory
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  • For correspondence: anurag.hs86@gmail.com
Zainab Zaidi
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: znbzaidi14@gmail.com
Rohan Dandage
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: rraadd_8@hotmail.com
Dhanasekaran Shanmugam
2 CSIR-National Chemical Laboratory
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  • For correspondence: d.shanmugam@ncl.res.in
Kausik Chakraborty
1 CSIR-Institute of Genomics and Integrative Biology;
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  • For correspondence: kausik@igib.in
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Abstract

Changes in metabolism can alter the cellular milieu; can this also change intracellular proteostasis? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change proteostasis, arguably, it should also alter mutational buffering. Building on this, we find that altered cellular metabolic states in E. coli buffer distinct mutations. Buffered-mutants had folding problems in vivo and were differently chaperoned in different metabolic states. Notably, this assistance was dependent upon the metabolites and not on the increase in canonical chaperone machineries. Additionally, we were able to reconstitute the folding assistance afforded by metabolites in vitro and propose that changes in metabolite concentrations have the potential to alter proteostasis. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in positive or negative regulation of proteostasis.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 06, 2019.
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Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
Kanika Verma, Kanika Saxena, Rajashekar Donaka, Aseem Chaphalkar, Manish Kumar Rai, Anurag Shukla, Zainab Zaidi, Rohan Dandage, Dhanasekaran Shanmugam, Kausik Chakraborty
bioRxiv 540039; doi: https://doi.org/10.1101/540039
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Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
Kanika Verma, Kanika Saxena, Rajashekar Donaka, Aseem Chaphalkar, Manish Kumar Rai, Anurag Shukla, Zainab Zaidi, Rohan Dandage, Dhanasekaran Shanmugam, Kausik Chakraborty
bioRxiv 540039; doi: https://doi.org/10.1101/540039

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