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Cell Autonomous Energy & Nutrient Sensing Pathways.docx

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Jeff Stuart

Cell Autonomous EnergyNutrient Sensing PathwaysMarch2614929 AM PGC1and AMP kinaselongterm maintenance of intracellular ATP levelsInsulinlike growth factor1 IGF1 and mammalian target of rapamycin mTORnutrient signaling pathwaysMitochondrial volume density the more mitochondria in a cell the more metabolically active the cell isHave a process of making or degrading mitochondriaEspecially in the skeletal muscleMitophagy is a little less known so we arent going to be talking about it PGC1and AMP Kinaselongterm maintenance of intracellular ATP levelsAdaptation to changing metabolic demandShort term changes to change in ATP useIncrease flux through ox phosIncreased flux through anaerobic glycolysisDone through the same machinery but it will be working harderLong term responsesMore metabolic machinery mitochondria transporters enzymes Mitochondrial BiogenesisChronic high cellular metabolic rate stimulates mitochondrial biogenesisWhat stimulates mitochondrial biogenesis Mitochondrion contains 1500 unique protein13 encoded by mtDNA1487 encoded by nuclear DNARequires coordinated regulation of nuclear and mitochondrial gene transcription NRF1NRF2 nuclearencoded mitochondrial proteinsmtTFA TFAM mtDNAencoded mitochondrial proteinsNRF nuclear respiratory factor Both regulated by PGC1 not a transcription factor but interacts with other transcription factors Discovery of PGC1 alpha regulation of mitochondrial biogenesis in cold acclimated small mammalsRemember mitochondrial content of BAT cells increases overtime in coldexposed animalsWeeks in cold acclimation vs BAT mitochondrial yield PGC1 alpha mRNA in mouse tissue in response to cold exposureUCP1 is always regulatedNot at normal temperature at room temperature prefer to be at 38 CThis means for sure in this case that there is more of this protein presentThe white fat and liver are negative controls not expressed in these tissues PGC1 alpha KO mouse cannot tolerate cold
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