PHEMDD · Phosphate homeostasis and energy metabolism in Dictyostelium discoideum
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-07-01 → 2019-06-30
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Phosphate homeostasis and energy metabolism in Dictyostelium discoideum
In all living systems, homeostasis maintains constancy despite fluctuating environmental conditions. Inorganic phosphate (Pi) is an essential component of life for which the cellular concentration must be tightly controlled. Pi is incorporated in nucleic acids, proteins, lipids, and sugars, serving structural and signaling functions. It is also involved in energy metabolism since the high-energy bonds present in ATP, the main energy currency in the cell, are phosphoanhydride (Pi-Pi) bonds. Alterations in Pi homeostasis or in the levels of Pi storage form (polyphosphate) is linked to many pathological states including myopathy, cardiac dysfunction, platelet dysfunction, hyperparathyroidism, obesity, tumour formation, and cancer. There must then be a system that controls Pi homeostasis in concert with energy metabolism. One excellent candidate to act in such a system is the inositol pyrophosphates (PP-IPs). These are ubiquitously distributed highly phosphorylated molecules that have been described as metabolic messengers, being involved in many processes including cell signalling, gene transcription, growth, proliferation, and regulation of metabolic homeostasis. The purpose of this study is to understand Pi homeostasis by elucidating the relationships between Pi homeostasis, energy metabolism, and PP-IPs, using the social amoeba Dictyostelium discoideum as a model system.
Data: CORDIS, © European Union
Project objective
Adenosine triphosphate (ATP) is the universal biological energy currency. Its cellular concentration is tightly regulated and depends on rates of glycolysis, oxidative phosphorylation, and obviously on phosphate availability. How is phosphate concentration regulated as a function of the cell’s demands? Inositol pyrophosphates, described as metabolic messengers, are excellent candidates to orchestrate phosphate homeostasis and energy metabolism. The research programme proposed here aims to elucidate the relationships between phosphate homeostasis, energy metabolism, and inositol pyrophosphates using the amoeba Dictyostelium discoideum as a model system. This organism has high levels of inositol pyrophosphates and inorganic polyphosphate (polyP) and, surprisingly, a comparatively low level of ATP, suggesting that inositol pyrophosphates may serve as a phosphate reservoir for ATP production. I will use a combination of metabolomics analysis, steady-state and dynamic flux analysis of ATP, polyP, Pi and inositol pyrophosphate levels, and a functional analysis of mitochondria to evaluate the impact of polyP and inositol pyrophosphates on the metabolic/energetic state of this organism. I will investigate the function of polyP, which is induced during development, to understand how and why phosphate homeostasis is so dramatically modified during this process. This will be the first comprehensive analysis of the relationships between phosphate homeostasis and energy metabolism in eukaryotes.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union