Počet záznamů: 1
Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma
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SYSNO ASEP 0542429 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma Tvůrce(i) Špačková, Jitka (FGU-C) RID, ORCID
Gotvaldová, Klára (FGU-C) RID, ORCID
Dvořák, Aleš (FGU-C) ORCID, RID, SAI
Urbančoková, Alexandra (FGU-C) ORCID
Pospíšilová, K. (CZ)
Větvička, D. (CZ)
Leguina-Ruzzi, Alberto A. (FGU-C) RID, ORCID
Tesařová, P. (CZ)
Vítek, L. (CZ)
Ježek, Petr (FGU-C) RID, ORCID
Smolková, Katarína (FGU-C) RID, ORCID, SAIČíslo článku 1709 Zdroj.dok. Cancers (Basel). - : MDPI
Roč. 13, č. 7 (2021)Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova IDH2 ; 2HG ; ADHFE1 ; breast carcinoma Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP NV19-01-00101 GA MZd - Ministerstvo zdravotnictví GA21-01205S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000638370000001 EID SCOPUS 85103502769 DOI 10.3390/cancers13071709 Anotace Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes using genetic and pharmacological approaches, we demonstrated the existence of active competition between 2HG producing enzymes, i.e., IDH2 and ADHFE1. Moreover, we showed that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release in the urine of breast cancer patients undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/2072-6694/13/7/1709
Počet záznamů: 1