Mitochondrial Respiratory Defect Causes Dysfunctional Lactate Turnover via AMP-activated Protein Kinase Activation in Human-induced Pluripotent Stem Cell-derived Hepatocytes

Cited 8 time in webofscience Cited 0 time in scopus
  • Hit : 228
  • Download : 0
DC FieldValueLanguage
dc.contributor.authorIm, Ilkyunko
dc.contributor.authorJang, Mi jinko
dc.contributor.authorPark, Seung Juko
dc.contributor.authorLee, Sang Heeko
dc.contributor.authorChoi, Jin Hoko
dc.contributor.authorYoo, Han Wookko
dc.contributor.authorKim, Seyunko
dc.contributor.authorHan, Yong-Mahnko
dc.date.accessioned2016-04-22T07:47:23Z-
dc.date.available2016-04-22T07:47:23Z-
dc.date.created2015-12-23-
dc.date.created2015-12-23-
dc.date.issued2015-12-
dc.identifier.citationJOURNAL OF BIOLOGICAL CHEMISTRY, v.290, no.49, pp.29493 - 29505-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10203/205708-
dc.description.abstractA defective mitochondrial respiratory chain complex (DMRC) causes various metabolic disorders in humans. However, the pathophysiology of DMRC in the liver remains unclear. To understand DMRC pathophysiology in vitro, DMRC-induced pluripotent stem cells were generated from dermal fibroblasts of a DMRC patient who had a homoplasmic mutation (m.3398T -> C) in the mitochondrion-encoded NADH dehydrogenase 1 (MTND1) gene and that differentiated into hepatocytes (DMRC hepatocytes) in vitro. DMRC hepatocytes showed abnormalities in mitochondrial characteristics, the NAD(+)/NADH ratio, the glycogen storage level, the lactate turnover rate, and AMPK activity. Intriguingly, low glycogen storage and transcription of lactate turnover-related genes in DMRC hepatocytes were recovered by inhibition of AMPK activity. Thus, AMPK activation led to metabolic changes in terms of glycogen storage and lactate turnover in DMRC hepatocytes. These data demonstrate for the first time that energy depletion may lead to lactic acidosis in the DMRC patient by reduction of lactate uptake via AMPK in liver.-
dc.languageEnglish-
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC-
dc.subjectHEREDITARY OPTIC NEUROPATHY-
dc.subjectCOMPLEX I DEFICIENCY-
dc.subjectHUMAN SOMATIC-CELLS-
dc.subjectLACTIC-ACIDOSIS-
dc.subjectELECTRON-TRANSPORT-
dc.subjectDIABETES-MELLITUS-
dc.subjectHUMAN FIBROBLASTS-
dc.subjectSKELETAL-MUSCLE-
dc.subjectDEFINED FACTORS-
dc.subjectGENE-MUTATIONS-
dc.titleMitochondrial Respiratory Defect Causes Dysfunctional Lactate Turnover via AMP-activated Protein Kinase Activation in Human-induced Pluripotent Stem Cell-derived Hepatocytes-
dc.typeArticle-
dc.identifier.wosid000366613400032-
dc.identifier.scopusid2-s2.0-84949023840-
dc.type.rimsART-
dc.citation.volume290-
dc.citation.issue49-
dc.citation.beginningpage29493-
dc.citation.endingpage29505-
dc.citation.publicationnameJOURNAL OF BIOLOGICAL CHEMISTRY-
dc.identifier.doi10.1074/jbc.M115.670364-
dc.contributor.localauthorKim, Seyun-
dc.contributor.localauthorHan, Yong-Mahn-
dc.contributor.nonIdAuthorJang, Mi jin-
dc.contributor.nonIdAuthorLee, Sang Hee-
dc.contributor.nonIdAuthorChoi, Jin Ho-
dc.contributor.nonIdAuthorYoo, Han Wook-
dc.type.journalArticleArticle-
dc.subject.keywordPlusHEREDITARY OPTIC NEUROPATHY-
dc.subject.keywordPlusCOMPLEX I DEFICIENCY-
dc.subject.keywordPlusHUMAN SOMATIC-CELLS-
dc.subject.keywordPlusLACTIC-ACIDOSIS-
dc.subject.keywordPlusELECTRON-TRANSPORT-
dc.subject.keywordPlusDIABETES-MELLITUS-
dc.subject.keywordPlusHUMAN FIBROBLASTS-
dc.subject.keywordPlusSKELETAL-MUSCLE-
dc.subject.keywordPlusDEFINED FACTORS-
dc.subject.keywordPlusGENE-MUTATIONS-
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 8 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0