27 research outputs found

    l-Arginine Metabolism Impairment in Sepsis and Diseases: Causes and Consequences

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    International audienceSepsis is recognized as a common cause for admission in ICUs. In general, sepsis and many diseases lead to alterations of the metabolism of amino acids (AA), among them arginine (Ventura et al. Amino Acids 39:1417–1426, 2010) more especially. Indeed, in humans, sepsis is characterized by a substantial decrease in arginine pools. This decrease of arginine concentration is usually due to a major increase of its consumption and a decrease of its endogenous production leading to the concept of “arginine deficiency” (Ventura et al. Amino Acids 39:1417–1426, 2010). Hence, in sepsis, it is generally admitted that endogenous synthesis (i.e., arginine is a non-essential amino acid) cannot meet the needs and arginine becomes a conditionally essential AA (Pribis et al. JPEN J Parenter Enteral Nutr 36:53–59, 2012). This may have important consequences. As a matter of fact, arginine is not only a component of proteins but also a molecule that can generate a number of active metabolites (Fig. 12.1): arginine may be the precursor of nitric oxide (NO, which is essential for the immune system), of ornithine (which is recognized as a polyamine precursor), or of agmatine (which is a major regulator of cell functions). Moreover, arginine is an important element in muscle energy: after reacting with glycine and methionine, it allows the formation of creatine. Finally, arginine acts as a secretagogue (such as insulin, glucagon, growth hormones, prolactin, and catecholamines) (Wu. Amino Acids 37:1–17, 2009). This could explain why the impairment of arginine homeostasis in sepsis and several diseases can contribute to pathophysiological alterations

    Mitochondrial membrane remodelling regulated by a conserved rhomboid protease.

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    Rhomboid proteins are intramembrane serine proteases that activate epidermal growth factor receptor (EGFR) signalling in Drosophila. Rhomboids are conserved throughout evolution, and even in eukaryotes their existence in species with no EGFRs implies that they must have additional roles. Here we report that Saccharomyces cerevisiae has two rhomboids, which we have named Rbd1p and Rbd2p. RBD1 deletion results in a respiratory defect; consistent with this, Rbd1p is localized in the inner mitochondrial membrane and mutant cells have disrupted mitochondria. We have identified two substrates of Rbd1p: cytochrome c peroxidase (Ccp1p); and a dynamin-like GTPase (Mgm1p), which is involved in mitochondrial membrane fusion. Rbd1p mutants are indistinguishable from Mgm1p mutants, indicating that Mgm1p is a key substrate of Rbd1p and explaining the rbd1Delta mitochondrial phenotype. Our data indicate that mitochondrial membrane remodelling is regulated by cleavage of Mgm1p and show that intramembrane proteolysis by rhomboids controls cellular processes other than signalling. In addition, mitochondrial rhomboids are conserved throughout eukaryotes and the mammalian homologue, PARL, rescues the yeast mutant, suggesting that these proteins represent a functionally conserved subclass of rhomboid proteases
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