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Cytochrome c Oxidase Subunit 4 Isoform Exchange Results in Modulation of Oxygen Affinity
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SYSNO ASEP 0524126 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cytochrome c Oxidase Subunit 4 Isoform Exchange Results in Modulation of Oxygen Affinity Author(s) Pajuelo-Reguera, David (FGU-C) RID, ORCID, SAI
Čunátová, Kristýna (FGU-C) RID, ORCID
Vrbacký, Marek (FGU-C) RID, ORCID
Pecinová, Alena (FGU-C) RID, ORCID, SAI
Houštěk, Josef (FGU-C) RID, ORCID
Mráček, Tomáš (FGU-C) RID, ORCID
Pecina, Petr (FGU-C) RID, ORCIDArticle number 443 Source Title Cells. - : MDPI
Roč. 9, č. 2 (2020)Number of pages 19 s. Language eng - English Country CH - Switzerland Keywords mitochondria ; OXPHOS ; respiratory chain ; cytochrome c oxidase ; COX ; COX4 isoforms ; COX4i2 ; oxygen affinity ; p(50) ; oxygen sensing Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA16-13671S GA ČR - Czech Science Foundation (CSF) NV17-28784A GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000521944900184 DOI 10.3390/cells9020443 Annotation Cytochrome c oxidase (COX) is regulated through tissue-, development- or environment-controlled expression of subunit isoforms. The COX4 subunit is thought to optimize respiratory chain function according to oxygen-controlled expression of its isoforms COX4i1 and COX4i2. However, biochemical mechanisms of regulation by the two variants are only partly understood. We created an HEK293-based knock-out cellular model devoid of both isoforms (COX4i1/2 KO). Subsequent knock-in of COX4i1 or COX4i2 generated cells with exclusive expression of respective isoform. Both isoforms complemented the respiratory defect of COX4i1/2 KO. The content, composition, and incorporation of COX into supercomplexes were comparable in COX4i1- and COX4i2-expressing cells. Also, COX activity, cytochrome c affinity, and respiratory rates were undistinguishable in cells expressing either isoform. Analysis of energy metabolism and the redox state in intact cells uncovered modestly increased preference for mitochondrial ATP production, consistent with the increased NADH pool oxidation and lower ROS in COX4i2-expressing cells in normoxia. Most remarkable changes were uncovered in COX oxygen kinetics. The p(50) (partial pressure of oxygen at half-maximal respiration) was increased twofold in COX4i2 versus COX4i1 cells, indicating decreased oxygen affinity of the COX4i2-containing enzyme. Our finding supports the key role of the COX4i2-containing enzyme in hypoxia-sensing pathways of energy metabolism. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2021 Electronic address https://www.mdpi.com/2073-4409/9/2/443
Number of the records: 1