IF1 AND CELL DEATH · Expression and function of the endogenous inhibitor of the mitochondrial F1F0-ATPase, IF-1, and its role in shaping the cellular response during ischaemia and cell death
6РП — Действия „Мария Кюри“
- Период
- 2005-11-01 → 2007-10-31
- Финансиране от ЕС
- 159 613 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Протеинът IF-1 действа като „спирачка“, която пречи на митохондриите да изразходват енергия при недостиг на кислород, например по време на инсулт или сърдечен удар. Разбирането на неговата функция помага да се разбере как клетките се предпазват от увреждания и как се регулира енергията им.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - IF1 AND CELL DEATH (Expression and function of the endogenous inhibitor of the mitochondrial F1F0-ATPase, IF-1, and its role during ischaemia)
Mitochondria are microscopic structures within cells that are essential for normal cell function. They house the machinery required to use oxygen and to create molecules that can be used to power energy dependent processes, such as muscle contraction, firing nerve impulses, secreting hormones etc. Indeed, the only reason we have to breathe oxygen is to provide our mitochondria with oxygen to carry out these fundamental reactions. Under conditions in which mitochondria do not have sufficient supply of oxygen, such as during episodes of hypoxia, during a stroke or a heart attack, mitochondrial reactions may reverse so that they use up the energy providing molecules rather than generate them. Cells make a protein that is thought to act as a brake to this mechanism, known as the endogenous inhibitor factor or IF-1. As almost all information on this protein is based on biochemical experiments, and almost nothing is known about its behaviour within the cell, we have explored its actions in living cells. We have been able to manipulate the expression of the protein and using fluorescent indicators and fluorescence microscopy, have explored its impact both on normal mitochondrial function and on the response to hypoxia. We have established that the protein significantly protects cells from hypoxic injury and helps to preserve energy state of the cell. We also had some surprising results that suggest that the protein is a profound modulator of normal mitochondrial function, increasing the numbers of mitochondria in cells, increasing the efficiency by which they make energy rich molecules and altering mitochondrial structure. This is the first time that there has been any suggestion that the protein has any role to play in normal mitochondrial function. This leads to all sorts of interesting questions about the relative expression of the protein in different cell types and to further explorations of the role of the protein as a determinant of mitochondrial function. This is potentially very important, as mitochondria are different in different tissues; their efficiency, structure and density all vary, as does their vulnerability to injury. Understanding the factors that dictate these differences may help us to understand why some tissues are more vulnerable to hypoxic injury than others.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
ATP fuels all cellular processes and is fundamental for life and well-being. Mitochondria, which play a central role in cell regulation, are the principal source of cellular ATP. It is increasingly clear that defects in mitochondrial function underlie many major diseases (e.g. of the heart and central nervous system).The ATP produced by mitochondria is synthesised by the F1-F0 ATP synthase. The enzyme is a proton motive ATPase, which is driven as an ATP synthase by the proton motive force, expressed primarily as a potential. If the potential collapses, e.g. under pathological conditions such as anoxia, the enzyme reverts from ATP synthesis to ATP hydrolysis, glycolysis becomes the only source of cellular ATP and mitochondria act as ATP consumers.IF-1 is a protein, which inhibits ATPase activity. It binds the F1 sector of the ATPase, limits its hydrolytic activity and so protects the cell from ATP depletion. IF-1 is therefore a key determinant of cell survival during potentially lethal events such as ischemia, a major cause of death in industrialized countries. Furthermore, as the pathway of cell death to apoptosis or to necrotic cell death depends on ATP availability, IF-1 may play an important role in defining the pathway to cell death.Remarkably, despite extensive and detailed knowledge IF-1 at a molecular level little is known about its comparative cell physiology between cell types and between species. The aim of my research training at the Physiology Department of the University College London is to characterize the functional contribution of IF-1 in physiological and pathological conditions.Specifically, we plan- to examine IF-1 expression and localization in different tissues and different species- to use molecular biological techniques to generate recombinant probes of IF-1- to examine the physiological and pathological consequences of alterations of IF-1 gene expression.- Finally, to asses the role of IF-1 in cell death and tumourigenesis.
Оригинален текст от CORDIS (на английски).
Участници
- DEPARTMENT OF PHYSIOLOGY, UNIVERSITY COLLEGE LONDON · LONDONКоординаторНиво градОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз