H2020Индивидуална стипендия2017–2019

PHEMDD · Phosphate homeostasis and energy metabolism in Dictyostelium discoideum

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-07-01 → 2019-06-30
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между фосфатния баланс, енергийния обмен и молекулите PP-IP се изучава чрез модел с социални амеби. Разбирането на тези процеси е важно, тъй като нарушенията в нивата на фосфата са свързани с заболявания като затлъстяване, сърдечна дисфункция и рак.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY COLLEGE LONDON · LondonКоординаторОбединеното кралство