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Lactate dehydrogenase activity drives hair follicle stem cell activation

Flores, Aimee ; Schell, John ; Krall, Abigail S ; Jelinek, David ; Miranda, Matilde ; Grigorian, Melina ; Braas, Daniel ; White, Andrew C ; Zhou, Jessica L ; Graham, Nicholas A ; Graeber, Thomas ; Seth, Pankaj ; Evseenko, Denis ; Coller, Hilary A ; Rutter, Jared ; Christofk, Heather R ; Lowry, William E

Nature cell biology, 2017-09, Vol.19 (9), p.1017-1026 [Periódico revisado por pares]

England: Nature Publishing Group

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Lactate dehydrogenase activity drives hair follicle stem cell activation
Autor: Flores, Aimee ; Schell, John ; Krall, Abigail S ; Jelinek, David ; Miranda, Matilde ; Grigorian, Melina ; Braas, Daniel ; White, Andrew C ; Zhou, Jessica L ; Graham, Nicholas A ; Graeber, Thomas ; Seth, Pankaj ; Evseenko, Denis ; Coller, Hilary A ; Rutter, Jared ; Christofk, Heather R ; Lowry, William E
Assuntos: Acrylates - pharmacology ; Animals ; Anion Transport Proteins - antagonists & inhibitors ; Anion Transport Proteins - genetics ; Anion Transport Proteins - metabolism ; Cell activation ; Cell metabolism ; Cell Proliferation - drug effects ; Cellular Senescence - drug effects ; Clonal deletion ; Dehydrogenase ; Dehydrogenases ; Epidermis ; Female ; Genetic aspects ; Genotype ; Glycolysis ; Glycolysis - drug effects ; Hair ; Hair Follicle - cytology ; Hair Follicle - drug effects ; Hair Follicle - enzymology ; Hair follicles ; Health aspects ; Isoenzymes - deficiency ; Isoenzymes - genetics ; Isoenzymes - metabolism ; L-Lactate dehydrogenase ; L-Lactate Dehydrogenase - deficiency ; L-Lactate Dehydrogenase - genetics ; L-Lactate Dehydrogenase - metabolism ; Lactate dehydrogenase ; Lactate Dehydrogenase 5 ; Lactic acid ; Lactic Acid - metabolism ; Male ; Metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria ; Mitochondrial Membrane Transport Proteins - antagonists & inhibitors ; Mitochondrial Membrane Transport Proteins - genetics ; Mitochondrial Membrane Transport Proteins - metabolism ; Monocarboxylic Acid Transporters ; Myc protein ; Phenotype ; Proto-Oncogene Proteins c-myc - metabolism ; Pyruvic acid ; Signal Transduction ; Stem cells ; Stem Cells - drug effects ; Stem Cells - enzymology ; Time Factors
É parte de: Nature cell biology, 2017-09, Vol.19 (9), p.1017-1026
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Lactate dehydrogenase activity drives hair follicle stem cell activation

England: Nature Publishing Group

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