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Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study
Journal article   Open access   Peer reviewed

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

Mariona Guitart-Mampel, Pedro Urquiza, Fausto Carnevale Neto, James R. Anderson, Vedangi Hambardikar, Ernest R. Scoma, Gennifer E. Merrihew, Lu Wang, Michael J. MacCoss, Daniel Raftery, …
Frontiers in cell and developmental biology, v 10, p833127
17 Feb 2022
PMID: 35252194
url
https://doi.org/10.3389/fcell.2022.833127View
Published, Version of Record (VoR) Open

Abstract

Cell and Developmental Biology
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 these organisms, polyP shows a co-localization with mitochondria, and its role as a key regulator of the stress responses, including the maintenance of appropriate 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 have conducted a comprehensive study of the status of cellular physiology, using proteomics and metabolomics approaches. Our results suggest a clear dysregulation of mitochondrial physiology, especially of bioenergetics, in MitoPPX cells when compared with Wt cells. Moreover, the effects induced by the enzymatic depletion of polyP are similar to those present in the mitochondrial dysfunction that is observed in neurodegenerative disorders and in neuronal aging. Based on our findings, the metabolism of mitochondrial polyP could be a valid and innovative pharmacological target in these conditions.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Developmental Biology
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