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Oxygen and calcium metabolism and their relationship with cellular life and death


Up to 2% of the oxygen consumed by the mitochondrial respiratory chain suffers monoeletronic reduction, mostly at the level of the semiquinone form of coenzyme Q, leading to the generation of the superoxide radical, which can in turn produce other reactive oxygen species, such as hydrogen peroxide and the hydroxyl radical. Under situations in which mitochondrial generation of reactive oxygen species is increased, or the mitochondrial antioxidant defense mechanisms are impared, these reactive oxygen species may accumulate and lead to irreversible damage of mitochondrial DNA, membrane lipids and proteins, resulting in mitochondrial dysfunction and consequent cell death. In this project, we propose to study the mechanisms by which Ca2+ stimulates mitochondrial reactive oxygen species generation, detailing the consequences of these species on different mitochondrial components. We also plan to investigate new mechanisms by which cells defend themselves against mitochondrial oxidative stress and drugs that may prevent mitochondrial injury induced by reactive oxygen species in isolated mitochondria, intact cells, tissues and organs in vivo. In addition, we propose to study calcium homeostasis and mitochondrial bioenergetics in emergent pathogenic fungi with the aim to better understand their physiology and may contribute to the development of more effective chemotherapy against these opportunistic pathogens. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JARMUSZKIEWICZ‚ W.; MILANI‚ G.; FORTES‚ F.; SCHREIBER‚ A.Z.; SLUSE‚ F.E.; VERCESI‚ A.E.. First evidence and characterization of an uncoupling protein in fungi kingdom: CpUCP of Candida parapsilosis. FEBS Letters, v. 467, n. 2, p. 145-149, . (98/13012-5)
R.A. CAVALHEIRO; F. FORTES; J. BORECKÝ; V.C. FAUSTINONI; A.Z. SCHREIBER. Respiration, oxidative phosphorylation, and uncoupling protein in Candida albicans. Brazilian Journal of Medical and Biological Research, v. 37, n. 10, p. 1455-1461, . (98/13012-5)
MILANI‚ G.; SCHEREIBER‚ A.Z.; VERCESI‚ A.E.. Ca< sup> 2+ transport into an intracellular acidic compartment of< i> Candida parapsilosis. FEBS Letters, v. 500, n. 1, p. 80-84, . (98/13012-5)

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