Biochimica et biophysica acta
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Biochim. Biophys. Acta · Jun 2015
Skeletal muscle mitochondria of NDUFS4-/- mice display normal maximal pyruvate oxidation and ATP production.
Mitochondrial ATP production is mediated by the oxidative phosphorylation (OXPHOS) system, which consists of four multi-subunit complexes (CI-CIV) and the FoF1-ATP synthase (CV). Mitochondrial disorders including Leigh Syndrome often involve CI dysfunction, the pathophysiological consequences of which still remain incompletely understood. Here we combined experimental and computational strategies to gain mechanistic insight into the energy metabolism of isolated skeletal muscle mitochondria from 5-week-old wild-type (WT) and CI-deficient NDUFS4-/- (KO) mice. ⋯ Several of the predicted changes were previously observed in experimental models of CI-deficiency. Interestingly, model predictions further suggested that CI deficiency only has major metabolic consequences when its activity decreases below 90% of normal levels, compatible with a biochemical threshold effect. Taken together, our results suggest that mouse skeletal muscle mitochondria possess a substantial CI overcapacity, which minimizes the effects of CI dysfunction on mitochondrial metabolism in this otherwise early fatal mouse model.
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Biochim. Biophys. Acta · Jun 2015
The Ferritin-Heavy-Polypeptide-Like-17 (FTHL17) gene encodes a ferritin with low stability and no ferroxidase activity and with a partial nuclear localization.
Three functional ferritin genes have been identified so far in mammals, and they encode the cytosolic Heavy (FTH) and Light chain (FTL) and the mitochondrial ferritin. The expression of a transcript by a fourth ferritin-like gene (Ferritin-Heavy-Polypeptide-Like-17, FTHL17) on the X chromosome was reported in mouse spermatogonia and in early embryonic cells. ⋯ The work confirms the presence of a fourth functional human ferritin gene with properties distinct from the canonical cytosolic ones.
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Biochim. Biophys. Acta · Jun 2015
ReviewAdvances in Phos-tag-based methodologies for separation and detection of the phosphoproteome.
This review article describes analytical techniques based on the phosphate-binding tag molecule "Phos-tag", which is an alkoxide-bridged dinuclear metal complex with 1,3-bis(pyridin-2-ylmethylamino)propan-2-olate, for studying the protein phosphorylome. The dinuclear zinc(II) complex forms a stable 1:1 complex with a phosphate monoester dianion in an aqueous solution under conditions of neutral pH. By using a series of functional Phos-tag derivatives, our group has developed novel techniques that are useful in studies on kinomics and phosphoproteomics. ⋯ Conventional mass spectrometry-based shotgun techniques used in phosphoproteomics detect the phosphorylation modification of proteins in peptide fragments, whereas the Phos-tag electrophoresis technique permits the direct analysis of the phosphorylation status of full-length proteins. The technique therefore provides a greater understanding of the detailed properties of particular proteins involved in specific physiological and pathological events. This article is part of a Special Issue entitled: Medical Proteomics.
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Biochim. Biophys. Acta · Jun 2015
Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice.
Consumption of high fat diet and insulin resistance induce significant changes in pancreatic islet morphology and function essential for maintenance of normal glucose homeostasis. We have used incretin receptor null mice to evaluate the role of gastric inhibitory polypeptide (GIP) in this adaptive response. ⋯ These data suggest that GIP released from islet alpha-cells and intestinal K-cells plays an important role in islet adaptations to high fat feeding.