Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity
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Date
2023-03-14
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Abstract
Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent.
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Funding Information: This research was funded by the European Union’s Horizon 2020 research and innovation program project FAT4BRAIN under grant agreement No. 857394 and by Latvian Institute of Organic Synthesis internal student grants IG-2022-04 and IG-2023-04 (to D.Z.-G.). Publisher Copyright: © 2023 by the authors.
Keywords
Fatty Acid Binding Protein 3/metabolism, Fatty Acid-Binding Proteins/metabolism, Fatty Acids pharmacology, Carnitine, Myocytes, Cardiac metabolism, isothermal titration calorimetry, long-chain acylcarnitines, 1.6 Biological sciences, 3.1 Basic medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database
Citation
Zelencova-Gopejenko, D, Videja, M, Grandane, A, Pudnika-Okinčica, L, Sipola, A, Vilks, K, Dambrova, M, Jaudzems, K & Liepinsh, E 2023, 'Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity', International Journal of Molecular Sciences, vol. 24, no. 6, 5528. https://doi.org/10.3390/ijms24065528