Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coenzyme Q10 (CoQ10) deficiency is associated to a variety of clinical phenotypes including neuromuscular and nephrotic disorders. We report two unrelated boys presenting encephalopathy, ataxia, and lactic acidosis, who died with necrotic lesions in different areas of brain. Levels of CoQ10 and complex II+III activity were increased in both skeletal muscle and fibroblasts, but it was a consequence of higher mitochondria mass measured as citrate synthase. In fibroblasts, oxygen consumption was also increased, whereas steady state ATP levels were decreased. Antioxidant enzymes such as NQO1 and MnSOD and mitochondrial marker VDAC were overexpressed. Mitochondria recycling markers Fis1 and mitofusin, and mtDNA regulatory Tfam were reduced. Exome sequencing showed mutations in PDHA1 in the first patient and in PDHB in the second. These genes encode subunits of pyruvate dehydrogenase complex (PDH) that could explain the compensatory increase of CoQ10 and a defect of mitochondrial homeostasis. These two cases describe, for the first time, a mitochondrial disease caused by PDH defects associated with unbalanced of both CoQ10 content and mitochondria homeostasis, which severely affects the brain. Both CoQ10 and mitochondria homeostasis appears as new markers for PDH associated mitochondrial disorders.
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PMID:Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q10 content. 2601 31

Winter survival for many animal species depends freeze tolerance, a capacity to endure the conversion of as much as 65-70% of total body water into extracellular ice while reorganizing metabolism to provide cells with cryoprotection against insults that include prolonged ischemia and hyperosmotic stress. Natural freeze tolerance involves not just de novo preservation mechanisms such as synthesis of high levels of cryoprotectants or novel proteins that manage ice formation, but also requires attention to and co-ordination of many cellular processes. The present review examines recent studies of the freeze-tolerant wood frog (Rana sylvatica) that probed previously unexplored areas of metabolic adaptation for freezing survival, with a particular emphasis on mitochondria. Post-translational controls on enzyme function play a prominent role in resculpting metabolic responses of the wood frog to freezing including reversible phosphorylation control over fuel processing at the pyruvate dehydrogenase locus and modulation of antioxidant defense enzymes (Mn-SOD, catalase). Enzymes involved in mitochondrial nitrogen metabolism (glutamate dehydrogenase, carbamoyl phosphate synthetase) are also differentially regulated during freezing but by different post-translational modifications including ADP-ribosylation, lysine acetylation or glutarylation. The action of microRNAs in mediating post-translational controls on gene expression aid the suppression of energy-expensive (cell cycle) or destructive (apoptosis) processes in the frozen state while also providing storage of transcripts that will be immediately available for repair or reactivation of metabolic processes after thawing. The effects of low temperature in strengthening mRNA-microRNA interactions can also provide a passive mechanism of metabolic suppression in the frozen state.
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PMID:Mitochondria, metabolic control and microRNA: Advances in understanding amphibian freeze tolerance. 3102 12