Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, Lithuania.
Department of Pharmacognosy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu pr. 13, LT-50166 Kaunas, Lithuania.
Cells. 2020 Feb 1;9(2):340. doi: 10.3390/cells9020340.
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. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent K value of mitochondria in cardiac fibers respiring on palmitoyl-l-carnitine or octanoyl-l-carnitine, but did not affect the high apparent K of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-l-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.
脂肪酸是心脏功能的主要呼吸底物，其在各种慢性疾病中发生改变。我们研究了脂肪酸氧化诱导的变化的机制及其与线粒体形态和 ADP/ATP 载体构象的关系，以探讨调节线粒体呼吸动力学的机制。饱和和不饱和、激活和未激活、长链和中链脂肪酸都能降低线粒体呼吸的表观 K 值。添加 5%葡聚糖 T-70 以模拟细胞质的膨胀压，显著增加了心脏纤维在棕榈酰肉碱或辛酰肉碱上呼吸时线粒体的低表观 K 值，但不影响丙酮酸和苹果酸呼吸时线粒体的高表观 K 值。电子显微镜显示，棕榈酰肉碱氧化诱导的线粒体超微结构变化（可被葡聚糖阻止）与羧基曲克芦丁诱导的变化相似。我们的数据表明，脂肪酸氧化诱导的 ADP/ATP 载体构象变化（M 态到 C 态，凝聚到标准线粒体）可能影响氧化磷酸化对 ADP 的亲和力。
