Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism have remained largely unknown. Our study demonstrates that cardiac-specific knockout of Phb2 leads to accumulation of lipid droplets and causes heart failure. Mechanistically, ablation of PHB2 impairs cardiac fatty acid oxidation (FAO) through downregulating carnitine palmitoyltransferase1b (CPT1b), a rate-limiting enzyme of cardiac mitochondrial FAO. Moreover, overexpression of CPT1b alleviates impaired FAO in PHB2-deficient cardiomyocytes. Thus, our study provides direct evidence for the link between PHB2 and cardiac fatty acid metabolism. Our study points out that PHB2 is a potential FAO regulator in cardiac mitochondrial inner membrane, as well as the connection between PHB2 and CPT1b and their relationships to cardiac pathology especially to cardiac fatty acid metabolic disorder.

中文翻译：

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抑制素2缺乏会损害心脏脂肪酸的氧化并导致心力衰竭。

脂肪酸是成人心脏能量产生的最主要底物来源。抑制素2（PHB2）是位于线粒体内膜上的高度保守的蛋白质，在细胞能量代谢稳态中起关键作用。然而，其在调节心脏脂肪酸代谢中的功能仍是未知的。我们的研究表明，心脏特异性Phb2的敲除导致脂质滴的积累并导致心力衰竭。从机制上讲，PHB2的消融通过下调肉毒碱棕榈酰转移酶1b（CPT1b）（一种心脏线粒体FAO的限速酶）来损害心脏脂肪酸氧化（FAO）。此外，CPT1b的过表达减轻了PHB2缺乏型心肌细胞中受损的FAO。因此，我们的研究为PHB2与心脏脂肪酸代谢之间的联系提供了直接证据。