Abstract
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 KmADP. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent KmADP value of mitochondria in cardiac fibers respiring on palmitoyl-l-carnitine or octanoyl-l-carnitine, but did not affect the high apparent KmADP 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.
Highlights
We investigated the mechanism of fatty acid–oxidation-induced changes and their relations with mitochondrial morphology and adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier conformation on the kinetics of the regulation of mitochondrial respiration in situ; i.e., in the mitochondria of saponin-permeabilized rat heart muscle fibers, where mitochondria and the ATPases in myofibrils and in the sarcoplasmic reticulum remain intact, corresponding to the physiological conditions in the cell [8,10]
We investigated which factors are responsible for the low apparent Km ADP
The results revealed that mitochondrial morphology in saponin-permeabilized cardiac fibers significantly alters during 5 min oxidation of palmitoyl-l-carnitine in the absence of dextran (Figure 12b); compared with pyruvate and malate oxidation (Figure 12a): increased mitochondrial intermembrane space and condensed mitochondrial matrix were observed
Summary
The major part of energy supply in cells comes from the fatty acid oxidation in mitochondria.Fatty acids as the main respiratory substrates are important, for cardiac function [1,2], and they recently have been shown to provide energy for the proliferation and survival of tumors [3].An increased fatty acid consumption reduces cardiac efficiency, and among the mechanisms involved, a modulation of the ADP/ATP carrier has been suggested [4,5,6].The studies of saponin-permeabilized heart and skeletal muscle fibers demonstrated that, in contrast to isolated mitochondria, the mitochondrial outer membrane in situ possesses a lowCells 2020, 9, 340; doi:10.3390/cells9020340 www.mdpi.com/journal/cellsCells 2020, 9, 340 permeability for exogenous ADP (high apparent Km ADP of oxidative phosphorylation for externalADP), and is crucial in the mechanism of regulation of mitochondrial respiration in vivo [7,8].Km ADP is drastically (up to 10-fold) decreased in the case of the oxidation of saturated fatty acids (CoAor carnitine-esters of palmitate and octanoate; alone or in combination with pyruvate), but not during the transport of fatty acids into mitochondria [9]; the mechanism of this phenomenon has not been elucidated yet.Mitochondria and intracellular ATPases in cardiomyocytes are in close proximity, and are arranged into tightly coupled structural and functional complexes known as intracellular, energetic units [8,10,11]. The major part of energy supply in cells comes from the fatty acid oxidation in mitochondria. Fatty acids as the main respiratory substrates are important, for cardiac function [1,2], and they recently have been shown to provide energy for the proliferation and survival of tumors [3]. An increased fatty acid consumption reduces cardiac efficiency, and among the mechanisms involved, a modulation of the ADP/ATP carrier has been suggested [4,5,6]. Km ADP is drastically (up to 10-fold) decreased in the case of the oxidation of saturated fatty acids (CoAor carnitine-esters of palmitate and octanoate; alone or in combination with pyruvate), but not during the transport of fatty acids into mitochondria [9]; the mechanism of this phenomenon has not been elucidated yet.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
