Dataset Information

Mitochondrial inorganic polyphosphate (polyP) is a contributor towards maintaining cellular bioenergetics in SH-SY5Y cells: a proteomics and metabolomics approach

ABSTRACT: Inorganic polyphosphate (polyP) is an ancestral, ubiquitous, and well-conserved polymer, which is present in all the studied organisms. It is formed by individual subunits of orthophosphate which are linked together by bonds structurally similar and isoenergetic to those found in ATP. While the metabolism and the physiological roles of polyP in some organisms, including bacteria and yeast, have already been described, the exact role of this polymer in mammalian physiology remains still poorly explored. In these organisms, polyP shows a co-localization with mitochondria. Accordingly, its role as a key regulator of bioenergetics has already been demonstrated by our group and others. Here, using Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) SH-SY5Y cells, we conducted a comprehensive study of the status of cellular physiology, using proteomics and metabolomics approaches. Our results suggested a clear dysregulation of mitochondrial physiology, especially of bioenergetics, in MitoPPX cells when compared with Wt. Interestingly, the effects induced by the enzymatically depletion of polyP are similar to those present in the mitochondrial dysfunction which is observed in neurodegenerative disorders and in neuronal aging. In fact, the role of polyP as a component of the cellular stress responses has already been proposed in diverse organisms, including mammals. Thereafter, our data could contribute to place the metabolism of mitochondrial polyP as a valid and innovative pharmacological target in these conditions.

ORGANISM(S): Homo Sapiens

SUBMITTER: Gennifer Merrihew

PROVIDER: PXD028185 | panorama | Wed Mar 16 00:00:00 GMT 2022

REPOSITORIES: PanoramaPublic

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Publications

Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study.

Guitart-Mampel Mariona M Urquiza Pedro P Carnevale Neto Fausto F Anderson James R JR Hambardikar Vedangi V Scoma Ernest R ER Merrihew Gennifer E GE Wang Lu L MacCoss Michael J MJ Raftery Daniel D Peffers Mandy J MJ Solesio Maria E ME

Frontiers in cell and developmental biology 20220217

Inorganic polyphosphate (polyP) is an ancient, ubiquitous, and well-conserved polymer which is present in all the studied organisms. It is formed by individual subunits of orthophosphate which are linked by structurally similar bonds and isoenergetic to those found in ATP. While the metabolism and the physiological roles of polyP have already been described in some organisms, including bacteria and yeast, the exact role of this polymer in mammalian physiology still remains poorly understood. In ...[more]

PMID: 35252194

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Project description:Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In Escherichia coli, ArcA (Aerobic Respiratory Control) helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in E. coli is well characterized; however, little is known about its role in anaerobically grown S. Typhimurium. Results: We compared the transcriptional profiles of the virulent wild-type (WT) strain (ATCC 14028s) and its isogenic arcA mutant grown under anaerobic conditions. We found that ArcA directly or indirectly regulates 392 genes (8.5% of the genome); of these, 138 genes are poorly characterized. Regulation by ArcA in S. Typhimurium is similar, but distinct from that in E. coli. Thus, genes/operons involved in core metabolic pathways (e.g., succinyl-CoA, fatty acid degradation, cytochrome oxidase complexes, flagellar biosynthesis, motility, and chemotaxis) were regulated similarly in the two organisms. However, genes/operons present in both organisms, but regulated differently by ArcA in S. Typhimurium included those coding for ethanolamine utilization, lactate transport and metabolism, and succinate dehydrogenases. Salmonella-specific genes/operons regulated by ArcA included those required for propanediol utilization, flagellar genes (mcpAC, cheV), Gifsy-1 prophage genes, and a few SPI-3 genes (mgtBC, slsA, STM3784). In agreement with our microarray data, the arcA mutant was non-motile, lacked flagella, and was as virulent in mice as the WT. Furthermore, we identified a set of 120 genes whose regulation was shared with the anaerobic redox regulator, Fnr. Conclusion(s): We have identified the ArcA regulon in anaerobically grown S. Typhimurium. Our results demonstrated that in S. Typhimurium, ArcA serves as a transcriptional regulator coordinating cellular metabolism, flagella biosynthesis, and motility. Furthermore, ArcA and Fnr share in the regulation of 120 S. Typhimurium genes.

Dataset Information

Mitochondrial inorganic polyphosphate (polyP) is a contributor towards maintaining cellular bioenergetics in SH-SY5Y cells: a proteomics and metabolomics approach

Publications

Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study.

Similar Datasets

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