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Angelini 2021 Cell Rep

From Bioblast
Publications in the MiPMap
Angelini A, Saha PK, Jain A, Jung SY, Mynatt RL, Pi X, Xie L (2021) PHDs/CPT1B/VDAC1 axis regulates long-chain fatty acid oxidation in cardiomyocytes. Cell Rep 37:109767.

ยป PMID: 34610308 Open Access

Angelini Aude, Saha Pradip K, Jain Antrix, Jung Sung Yun, Mynatt Randall L, Pi Xinchun, Xie Liang (2021) Cell Rep

Abstract: Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported in ischemic or late-stage failing hearts. The mechanism regulating this metabolic switch remains poorly understood. Here, we report that loss of PHD2/3, the cellular oxygen sensors, blocks LCFA mitochondria uptake and ฮฒ-oxidation in cardiomyocytes. In high-fat-fed mice, PHD2/3 deficiency improves glucose metabolism but exacerbates the cardiac defects. Mechanistically, we find that PHD2/3 bind to CPT1B, a key enzyme of mitochondrial LCFA uptake, promoting CPT1B-P295 hydroxylation. Further, we show that CPT1B-P295 hydroxylation is indispensable for its interaction with VDAC1 and LCFA ฮฒ-oxidation. Finally, we demonstrate that a CPT1B-P295A mutant constitutively binds to VDAC1 and rescues LCFA metabolism in PHD2/3-deficient cardiomyocytes. Together, our data identify an oxygen-sensitive regulatory axis involved in cardiac metabolism. โ€ข Keywords: Cardiac metabolism switch, Cardiomyocyte, Carnitine O-palmitoyltransferase 1b, Heart failure, Hypoxia, Long-chain fatty acid, Myocardial infarction, Prolyl hydroxylase domain protein, Voltage-dependent anion channel โ€ข Bioblast editor: Plangger M


Labels: MiParea: Respiration  Pathology: Cardiovascular  Stress:Ischemia-reperfusion 





2021-10