However, genes encoding subunits of the NADH dehydrogenase part of complex I are apparently missing in these species, so the complex might lack the NADH processing subunits. NADH dehydrogenase is an enzyme that converts nicotinamide adenine dinucleotide (NAD) from its reduced form (NADH) to its oxidized form (NAD ). Complex I is the first enzyme complex in the respiratory chain, and it accepts electrons from NADH+H+ derived from fat, carbohydrate, and amino acids to create an electrochemical gradient across the inner mitochondrial membrane. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). It is speculated that the chloroplast enzyme might use the quinone reductase function of the complex with a different reductant,- perhaps ferredoxin or NADPH. Lactate dehydrogenase (LDH) is an enzyme found in most living organisms responsible for the conversion of pyruvate, the end product of glycolysis, into lactic acid.With this conversion, the molecule also uses a unit of the energy transferring molecule NADH, releasing the hydrogen to produce NAD +, allowing glycolysis to continue. mTORC1 also controls synthesis of elongation factors, at the level of translation. Synonyms beta-NADH dehydrogenase dinucleotide activity, cytochrome c reductase activity, diaphorase activity, dihydrocodehydrogenase I dehydrogenase activity, dihydronicotinamide adenine dinucleotide dehydrogenase activity, diphosphopyridine diaphorase … The first complex to accept the donated electrons is NADH dehydrogenase. Whereas some groups have reported pronounced repression of 5′TOP mRNA translation by rapamycin [72, 73], others have found only a small or even no effect [67–69]. Second, a protein with no apparent functional domains called REDD1 (also known as DDIT4 and RTP801) can mediate inhibition of mTORC1 in response to hypoxic conditions in both flies and mammals [117, 118]. Nutrient signaling through amino acids involves RAG GTPases, which when activated cause mTORC1 to localize and interact with Rheb. In metabolism: The nature of the respiratory chain. There are three energy-transducing enzymes in the electron transport chain - NADH:ubiquinone oxidoreductase (complex I), Coenzyme Q – cytochrome c reductase (complex III), and cytochrome c oxidase (complex IV). For example, insulin has been shown to promote the activation of Akt at S473 by mTORC2 (Sarbassov et al., 2005). The GTP-bound form of Rheb directly interacts with mTORC1 and strongly stimulates its kinase activity. Rapamycin blocks Akt-induced SREBP-1 expression and nuclear accumulation, the expression of several lipogenic genes, and the synthesis of various classes of lipids . NX_O95139 - NDUFB6 - NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 - Function. HIF-driven transcription of BNIP3 and REDD1 have been described to inhibit mTORC1 under hypoxia (Fig. Can catalyze electron transfer from NADH to various electron acceptors which include, in addition to molecular oxygen, cytochrome c, 2,6 dichlorphenolindophenol, methylene blue, ferricyanide or P-nitroblue tetrazolium. Additionally, the antidiabetic drug, metformin, which is a known to activate adenosine monophosphate-activated protein kinase (AMPK) and also subsequently inhibits mTORC1, reduced hepatic lipid content by promoting fatty acid oxidation, impairing SREBP-1c expression and cleavage . TSC1/2 functions as a GTPase-activating protein for the Ras homolog enriched in brain (Rheb) GTPase. Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. mTORC1 integrates signals from nutrients, growth factors, energy, and stress to appropriately regulate key cellular responses including mRNA translation, lipid biogenesis, and autophagy. Complex I functions in the transfer of electrons from NADH to the respiratory chain. Recent studies identified mTORC1 as an upstream regulator of TFEB (Roczniak-Ferguson et al., 2012; Settembre et al., 2012; Martina et al., 2012; Pena-Llopis et al., 2011). However, it remains open whether S6K links mTORC1 to rDNA transcription in all cell types . Arginine-mediated activation of mTORC1 can occur upstream of the Rag GTPases through the lysosomal amino acid transporter SLC38A9 or cellular arginine sensor for mTORC1 (CASTOR1) (Rebsamen et al., 2015; Saxton et al., 2016; Wang et al., 2015). 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