Journal article
Enzymatic Depletion of Mitochondrial Inorganic Polyphosphate (polyP) Increases the Generation of Reactive Oxygen Species (ROS) and the Activity of the Pentose Phosphate Pathway (PPP) in Mammalian Cells
Antioxidants, v 11(4), 685
31 Mar 2022
PMID: 35453370
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Inorganic polyphosphate (polyP) is an ancient biopolymer that is well preserved throughout evolution and present in all studied organisms. In mammals, it shows a high co-localization with mitochondria, and it has been demonstrated to be involved in the homeostasis of key processes within the organelle, including mitochondrial bioenergetics. However, the exact extent of the effects of polyP on the regulation of cellular bioenergetics, as well as the mechanisms explaining these effects, still remain poorly understood. Here, using HEK293 mammalian cells under Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) conditions, we show that depletion of polyP within mitochondria increased oxidative stress conditions. This is characterized by enhanced mitochondrial O-2(-) and intracellular H2O2 levels, which may be a consequence of the dysregulation of oxidative phosphorylation (OXPHOS) that we have demonstrated in MitoPPX cells in our previous work. These findings were associated with an increase in basal peroxiredoxin-1 (Prx1), superoxide dismutase-2 (SOD2), and thioredoxin (Trx) antioxidant protein levels. Using C-13-NMR and immunoblotting, we assayed the status of glycolysis and the pentose phosphate pathway (PPP) in Wt and MitoPPX cells. Our results show that MitoPPX cells display a significant increase in the activity of the PPP and an increase in the protein levels of transaldolase (TAL), which is a crucial component of the non-oxidative phase of the PPP and is involved in the regulation of oxidative stress. In addition, we observed a trend towards increased glycolysis in MitoPPX cells, which corroborates our prior work. Here, for the first time, we show the crucial role played by mitochondrial polyP in the regulation of mammalian redox homeostasis. Moreover, we demonstrate a significant effect of mitochondrial polyP on the regulation of global cellular bioenergetics in these cells.
Metrics
1 Record Views
Details
- Title
- Enzymatic Depletion of Mitochondrial Inorganic Polyphosphate (polyP) Increases the Generation of Reactive Oxygen Species (ROS) and the Activity of the Pentose Phosphate Pathway (PPP) in Mammalian Cells
- Creators
- Vedangi Hambardikar - Rutgers, The State University of New JerseyMariona Guitart-Mampel - Rutgers, The State University of New JerseyErnest R. Scoma - Rutgers, The State University of New JerseyPedro Urquiza - Rutgers, The State University of New JerseyGowda G. A. Nagana - University of WashingtonDaniel Raftery - University of WashingtonJohn A. Collins - Thomas Jefferson UniversityMaria E. Solesio - Rutgers, The State University of New Jersey
- Publication Details
- Antioxidants, v 11(4), 685
- Publisher
- Mdpi
- Number of pages
- 18
- Grant note
- 1K99AG055701-01A1; 4R00AG055701-03 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Rutgers University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000785473900001
- Scopus ID
- 2-s2.0-85127388167
- Other Identifier
- 991022197450904721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
Source: SDGs in the Output
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Food Science & Technology