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



Guitart-Mampel, Mariona, Urquiza, Pedro, Carnevale Neto, Fausto, Anderson, James R ORCID: 0000-0003-0489-7997, Hambardikar, Vedangi, Scoma, Ernest R, Merrihew, Gennifer E, Wang, Lu, MacCoss, Michael J, Raftery, Daniel
et al (show 2 more authors) (2022) Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study. Frontiers in Cell and Developmental Biology, 10. 833127-.

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Abstract

<jats:p>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.</jats:p>

Item Type: Article
Uncontrolled Keywords: mitochondria, bioenergetics, mitochondrial metabolism, OXPHOS, inorganic polyphosphate, metabolomics, proteomics, SH-SY5Y cells
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 18 Feb 2022 11:25
Last Modified: 18 Jan 2023 21:12
DOI: 10.3389/fcell.2022.833127
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3149181