Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Int J Mol Sci. 2023 Aug 25;24(17):13188. doi: 10.3390/ijms241713188.
The heart requires a variety of energy substrates to maintain proper contractile function. Glucose and long-chain fatty acids (FA) are the major cardiac metabolic substrates under physiological conditions. Upon stress, a shift of cardiac substrate preference toward either glucose or FA is associated with cardiac diseases. For example, in pressure-overloaded hypertrophic hearts, there is a long-lasting substrate shift toward glucose, while in hearts with diabetic cardiomyopathy, the fuel is switched toward FA. Stromal interaction molecule 1 (STIM1), a well-established calcium (Ca) sensor of endoplasmic reticulum (ER) Ca store, is increasingly recognized as a critical player in mediating both cardiac hypertrophy and diabetic cardiomyopathy. However, the cause-effect relationship between STIM1 and glucose/FA metabolism and the possible mechanisms by which STIM1 is involved in these cardiac metabolic diseases are poorly understood. In this review, we first discussed STIM1-dependent signaling in cardiomyocytes and metabolic changes in cardiac hypertrophy and diabetic cardiomyopathy. Second, we provided examples of the involvement of STIM1 in energy metabolism to discuss the emerging role of STIM1 in the regulation of energy substrate preference in metabolic cardiac diseases and speculated the corresponding underlying molecular mechanisms of the crosstalk between STIM1 and cardiac energy substrate preference. Finally, we briefly discussed and presented future perspectives on the possibility of targeting STIM1 to rescue cardiac metabolic diseases. Taken together, STIM1 emerges as a key player in regulating cardiac energy substrate preference, and revealing the underlying molecular mechanisms by which STIM1 mediates cardiac energy metabolism could be helpful to find novel targets to prevent or treat cardiac metabolic diseases.
心脏需要多种能量底物来维持适当的收缩功能。葡萄糖和长链脂肪酸（FA）是生理条件下心脏代谢的主要底物。在应激状态下，心脏底物偏好向葡萄糖或 FA 的转变与心脏疾病有关。例如，在压力超负荷的肥厚心脏中，存在向葡萄糖的持久底物转变，而在糖尿病心肌病的心脏中，燃料则转向 FA。基质相互作用分子 1（STIM1）是内质网（ER）钙库的一种成熟的钙（Ca）传感器，越来越被认为是介导心脏肥大和糖尿病心肌病的关键因子。然而，STIM1 与葡萄糖/FA 代谢之间的因果关系以及 STIM1 参与这些心脏代谢疾病的可能机制尚不清楚。在这篇综述中，我们首先讨论了 STIM1 依赖性信号在心肌细胞中的作用以及心脏肥大和糖尿病心肌病中的代谢变化。其次，我们提供了 STIM1 参与能量代谢的例子，以讨论 STIM1 在代谢性心脏疾病中调节能量底物偏好的新兴作用，并推测 STIM1 与心脏能量底物偏好之间相互作用的潜在分子机制。最后，我们简要讨论并提出了靶向 STIM1 以拯救心脏代谢疾病的可能性。总之，STIM1 作为调节心脏能量底物偏好的关键因子之一，揭示 STIM1 介导心脏能量代谢的潜在分子机制，有助于寻找预防或治疗心脏代谢疾病的新靶点。
