Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae
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- dc.contributor.author Burgos, Raul
- dc.contributor.author Weber, Marc
- dc.contributor.author Martínez, Sira
- dc.contributor.author Lluch-Senar, Maria 1982-
- dc.contributor.author Serrano Pubull, Luis, 1982-
- dc.date.accessioned 2021-03-22T12:14:12Z
- dc.date.available 2021-03-22T12:14:12Z
- dc.date.issued 2020
- dc.description.abstract Protein degradation is a crucial cellular process in all-living systems. Here, using Mycoplasma pneumoniae as a model organism, we defined the minimal protein degradation machinery required to maintain proteome homeostasis. Then, we conditionally depleted the two essential ATP-dependent proteases. Whereas depletion of Lon results in increased protein aggregation and decreased heat tolerance, FtsH depletion induces cell membrane damage, suggesting a role in quality control of membrane proteins. An integrative comparative study combining shotgun proteomics and RNA-seq revealed 62 and 34 candidate substrates, respectively. Cellular localization of substrates and epistasis studies supports separate functions for Lon and FtsH. Protein half-life measurements also suggest a role for Lon-modulated protein decay. Lon plays a key role in protein quality control, degrading misfolded proteins and those not assembled into functional complexes. We propose that regulating complex assembly and degradation of isolated proteins is a mechanism that coordinates important cellular processes like cell division. Finally, by considering the entire set of proteases and chaperones, we provide a fully integrated view of how a minimal cell regulates protein folding and degradation.
- dc.description.sponsorship This work has been supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, under grant agreement 670216 (MYCOCHASSIS). We also acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Program from the Generalitat de Catalunya. M.W acknowledges the European Union’s Horizon 2020 research and innovation program under grant agreement 634942 (MycoSynVac) and M.L.‐S. The support from FEDER project from Instituto Carlos III (ISCIII, Acción Estratégica en Salud 2016) (reference CP16/00094). The proteomics analyses were performed in the CRG/UPF Proteomics Unit which is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech), and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D+i 2013‐2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF
- dc.format.mimetype application/pdf
- dc.identifier.citation Burgos R, Weber M, Martínez S, Lluch-Senar M, Serrano L. Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae. Mol Syst Biol. 2020 Dec;16(12):e9530. DOI: 10.15252/msb.20209530
- dc.identifier.doi http://dx.doi.org/10.15252/msb.20209530
- dc.identifier.issn 1744-4292
- dc.identifier.uri http://hdl.handle.net/10230/46886
- dc.language.iso eng
- dc.publisher Wiley Open Access
- dc.relation.ispartof Molecular Systems Biology. 2020 Dec;16(12):e9530
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
- dc.rights © 2020 Raul Burgos et al. Published under the terms of the CC BY 4.0 license
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.other Proteïnes
- dc.subject.other Proteòlisi
- dc.subject.other Genòmica
- dc.subject.other Mycoplasma pneumoniae
- dc.title Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion