Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase
Cytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP at high ATP/ADP-ratios. These bound ATP and ADP can be exchanged by cholate, which is generally used for the purification of CytOx...
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MDPI AG
2021-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/7/1579 |
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| author | Rabia Ramzan Jörg Napiwotzki Petra Weber Bernhard Kadenbach Sebastian Vogt |
| author_facet | Rabia Ramzan Jörg Napiwotzki Petra Weber Bernhard Kadenbach Sebastian Vogt |
| author_sort | Rabia Ramzan |
| collection | DOAJ |
| description | Cytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP at high ATP/ADP-ratios. These bound ATP and ADP can be exchanged by cholate, which is generally used for the purification of CytOx. Many crystal structures of isolated CytOx were performed with the enzyme isolated from mitochondria using sodium cholate as a detergent. Cholate, however, dimerizes the enzyme isolated in non-ionic detergents and induces a structural change as evident from a spectral change. Consequently, it turns off the “allosteric ATP-inhibition of CytOx”, which is reversibly switched on under relaxed conditions via cAMP-dependent phosphorylation and keeps the membrane potential and ROS formation in mitochondria at low levels. This cholate effect gives an insight into the structural-functional relationship of the enzyme with respect to ATP inhibition and its role in mitochondrial respiration and energy production. |
| first_indexed | 2024-03-10T10:10:05Z |
| format | Article |
| id | doaj.art-cbce9a196f3b4adc83e2644c40faaaea |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T10:10:05Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-cbce9a196f3b4adc83e2644c40faaaea2023-11-22T01:18:10ZengMDPI AGCells2073-44092021-06-01107157910.3390/cells10071579Cholate Disrupts Regulatory Functions of Cytochrome c OxidaseRabia Ramzan0Jörg Napiwotzki1Petra Weber2Bernhard Kadenbach3Sebastian Vogt4Biochemical-Pharmacological Center, Cardiovascular Research Laboratory, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, D-35043 Marburg, GermanyTheodor-Litt-Realschule, D-40593 Düsseldorf, GermanyBiochemical-Pharmacological Center, Cardiovascular Research Laboratory, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, D-35043 Marburg, GermanyDepartment of Chemistry, Philipps-University, D-35032 Marburg, GermanyBiochemical-Pharmacological Center, Cardiovascular Research Laboratory, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, D-35043 Marburg, GermanyCytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP at high ATP/ADP-ratios. These bound ATP and ADP can be exchanged by cholate, which is generally used for the purification of CytOx. Many crystal structures of isolated CytOx were performed with the enzyme isolated from mitochondria using sodium cholate as a detergent. Cholate, however, dimerizes the enzyme isolated in non-ionic detergents and induces a structural change as evident from a spectral change. Consequently, it turns off the “allosteric ATP-inhibition of CytOx”, which is reversibly switched on under relaxed conditions via cAMP-dependent phosphorylation and keeps the membrane potential and ROS formation in mitochondria at low levels. This cholate effect gives an insight into the structural-functional relationship of the enzyme with respect to ATP inhibition and its role in mitochondrial respiration and energy production.https://www.mdpi.com/2073-4409/10/7/1579cholatcytochrome c oxidaseATP binding siteregulatory functionallosteric ATP-Inhibition |
| spellingShingle | Rabia Ramzan Jörg Napiwotzki Petra Weber Bernhard Kadenbach Sebastian Vogt Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase Cells cholat cytochrome c oxidase ATP binding site regulatory function allosteric ATP-Inhibition |
| title | Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase |
| title_full | Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase |
| title_fullStr | Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase |
| title_full_unstemmed | Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase |
| title_short | Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase |
| title_sort | cholate disrupts regulatory functions of cytochrome c oxidase |
| topic | cholat cytochrome c oxidase ATP binding site regulatory function allosteric ATP-Inhibition |
| url | https://www.mdpi.com/2073-4409/10/7/1579 |
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