ArticleThe Biochemical journal2021
Depletion of mitochondrial inorganic polyphosphate (polyP) in mammalian cells causes metabolic shift from oxidative phosphorylation to glycolysis.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Inorganic polyphosphate chelates CaBiochemistry and biophysics reports · 2026Article
- From Food Additives to Neurodegeneration: The Emerging Role of Polyphosphates in Tauopathies.ACS chemical neuroscience · 2026Review
- Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection.Biomolecules · 2025Review
- Article
- Polyphosphate: a cellular Swiss army knife.Current opinion in biotechnology · 2025Review
- Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence.Aging cell · 2024Article
- Matrix Protein of Vesicular Stomatitis Virus Targets the Mitochondria, Reprograms Glucose Metabolism, and Sensitizes to 2-Deoxyglucose in Glioblastoma.Human gene therapy · 2024Article
- The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting.eLife · 2024Article
- Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.Physiology (Bethesda, Md.) · 2024Review
- The Protein Scaffolding Functions of Polyphosphate.Journal of molecular biology · 2024Review
- A mammalian model reveals inorganic polyphosphate channeling into the nucleolus and induction of a hyper-condensate state.Cell reports methods · 2024Article
- Inorganic polyphosphate and ion transport across biological membranes.Biochemical Society transactions · 2024Review
- The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non-small cell lung cancer H1299 cells.FEBS open bio · 2024Article
- Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle.Frontiers in cell and developmental biology · 2024Article
- Inorganic polyphosphate and the regulation of mitochondrial physiology.Biochemical Society transactions · 2023Article
- Evolutionary perspective on mammalian inorganic polyphosphate (polyP) biology.Biochemical Society transactions · 2023Review
- Human Prune Regulates the Metabolism of Mammalian Inorganic Polyphosphate and Bioenergetics.International journal of molecular sciences · 2023Article
- Lycopene Accumulation in Transgenic Mice Lacking One or Both Carotenoid Cleaving Enzymes.The Journal of nutrition · 2023Article
- Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.Frontiers in cell and developmental biology · 2023Article
- The Glacier Ice Worm,Biology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Inorganic polyphosphate (polyP) is a linear polymer composed of up to a few hundred orthophosphates linked together by high-energy phosphoanhydride bonds, identical with those found in ATP. In mammalian mitochondria, polyP has been implicated in multiple processes, including energy metabolism, ion channels function, and the regulation of calcium signaling. However, the specific mechanisms of all these effects of polyP within the organelle remain poorly understood. The central goal of this study was to investigate how mitochondrial polyP participates in the regulation of the mammalian cellular energy metabolism. To accomplish this, we created HEK293 cells depleted of mitochondrial polyP, through the stable expression of the polyP hydrolyzing enzyme (scPPX). We found that these cells have significantly reduced rates of oxidative phosphorylation (OXPHOS), while their rates of glycolysis were elevated. Consistent with this, metabolomics assays confirmed increased levels of metabolites involved in glycolysis in these cells, compared with the wild-type samples. At the same time, key respiratory parameters of the isolated mitochondria were unchanged, suggesting that respiratory chain activity is not affected by the lack of mitochondrial polyP. However, we detected that mitochondria from cells that lack mitochondrial polyP are more fragmented when compared with those from wild-type cells. Based on these results, we propose that mitochondrial polyP plays an important role as a regulator of the metabolic switch between OXPHOS and glycolysis.
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