Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria
Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid−oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier confo...
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/340 |
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| author | Adolfas Toleikis Sonata Trumbeckaite Julius Liobikas Neringa Pauziene Lolita Kursvietiene Dalia M. Kopustinskiene |
| author_facet | Adolfas Toleikis Sonata Trumbeckaite Julius Liobikas Neringa Pauziene Lolita Kursvietiene Dalia M. Kopustinskiene |
| author_sort | Adolfas Toleikis |
| collection | DOAJ |
| description | Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid−oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the regulation of mitochondrial respiration in rat skinned cardiac fibers. Saturated and unsaturated, activated and not activated, long and medium chain, fatty acids similarly decreased the apparent K<sub>m</sub><sup>ADP</sup>. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent K<sub>m</sub><sup>ADP</sup> value of mitochondria in cardiac fibers respiring on palmitoyl-<span style="font-variant: small-caps;">l</span>-carnitine or octanoyl-<span style="font-variant: small-caps;">l</span>-carnitine, but did not affect the high apparent K<sub>m</sub><sup>ADP</sup> of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-<span style="font-variant: small-caps;">l</span>-carnitine oxidation-induced changes in the mitochondrial ultrastructure (preventable by dextran) are similar to those induced by carboxyatractyloside. Our data suggest that a fatty acid oxidation-induced conformational change of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier (M-state to C-state, condensed to orthodox mitochondria) may affect the oxidative phosphorylation affinity for ADP. |
| first_indexed | 2024-03-12T05:48:49Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:48:49Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ab7d6cd726724f1b9f38095cf9c963c52023-09-03T05:23:08ZengMDPI AGCells2073-44092020-02-019234010.3390/cells9020340cells9020340Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart MitochondriaAdolfas Toleikis0Sonata Trumbeckaite1Julius Liobikas2Neringa Pauziene3Lolita Kursvietiene4Dalia M. Kopustinskiene5Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, LithuaniaNeuroscience Institute, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, LithuaniaNeuroscience Institute, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, LithuaniaInstitute of Anatomy, Lithuanian University of Health Sciences, Mickeviciaus 9, LT-44307 Kaunas, LithuaniaDepartment of Biochemistry, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, LithuaniaInstitute of Pharmaceutical Technologies, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50161 Kaunas, LithuaniaFatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid−oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the regulation of mitochondrial respiration in rat skinned cardiac fibers. Saturated and unsaturated, activated and not activated, long and medium chain, fatty acids similarly decreased the apparent K<sub>m</sub><sup>ADP</sup>. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent K<sub>m</sub><sup>ADP</sup> value of mitochondria in cardiac fibers respiring on palmitoyl-<span style="font-variant: small-caps;">l</span>-carnitine or octanoyl-<span style="font-variant: small-caps;">l</span>-carnitine, but did not affect the high apparent K<sub>m</sub><sup>ADP</sup> of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-<span style="font-variant: small-caps;">l</span>-carnitine oxidation-induced changes in the mitochondrial ultrastructure (preventable by dextran) are similar to those induced by carboxyatractyloside. Our data suggest that a fatty acid oxidation-induced conformational change of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier (M-state to C-state, condensed to orthodox mitochondria) may affect the oxidative phosphorylation affinity for ADP.https://www.mdpi.com/2073-4409/9/2/340adp/atp carrierk<sub>m</sub><sup>adp</sup>mitochondriafatty acid oxidationdextranmorphology |
| spellingShingle | Adolfas Toleikis Sonata Trumbeckaite Julius Liobikas Neringa Pauziene Lolita Kursvietiene Dalia M. Kopustinskiene Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria Cells adp/atp carrier k<sub>m</sub><sup>adp</sup> mitochondria fatty acid oxidation dextran morphology |
| title | Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria |
| title_full | Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria |
| title_fullStr | Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria |
| title_full_unstemmed | Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria |
| title_short | Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria |
| title_sort | fatty acid oxidation and mitochondrial morphology changes as key modulators of the affinity for adp in rat heart mitochondria |
| topic | adp/atp carrier k<sub>m</sub><sup>adp</sup> mitochondria fatty acid oxidation dextran morphology |
| url | https://www.mdpi.com/2073-4409/9/2/340 |
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