Murugasamy Krishnega, Munjal Aastha, Sundaresan Nagalingam Ravi
Cardiovascular and Muscle Research Laboratory, Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
Front Cardiovasc Med. 2022 Mar 18;9:850340. doi: 10.3389/fcvm.2022.850340. eCollection 2022.
The heart is a highly metabolically active organ that predominantly utilizes fatty acids as an energy substrate. The heart also derives some part of its energy by oxidation of other substrates, including glucose, lactose, amino acids and ketones. The critical feature of cardiac pathology is metabolic remodeling and loss of metabolic flexibility. Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins (SIRT1 to SIRT7), with NAD dependent deacetylase activity. SIRT3 is expressed in high levels in healthy hearts but downregulated in the aged or diseased hearts. Experimental evidence shows that increasing SIRT3 levels or activity can ameliorate several cardiac pathologies. The primary deacetylation targets of SIRT3 are mitochondrial proteins, most of which are involved in energy metabolism. Thus, SIRT3 improves cardiac health by modulating cardiac energetics. In this review, we discuss the essential role of SIRT3 in regulating cardiac metabolism in the context of physiology and pathology. Specifically, we summarize the recent advancements that emphasize the critical role of SIRT3 as a master regulator of cardiac metabolism. We also present a comprehensive view of all known activators of SIRT3, and elaborate on their therapeutic potential to ameliorate energetic abnormalities in various cardiac pathologies.
心脏是一个代谢高度活跃的器官，主要利用脂肪酸作为能量底物。心脏也通过氧化其他底物（包括葡萄糖、乳糖、氨基酸和酮体）来获取部分能量。心脏病理学的关键特征是代谢重塑和代谢灵活性丧失。沉默调节蛋白3（SIRT3）是七种哺乳动物沉默调节蛋白（SIRT1至SIRT7）之一，具有NAD依赖性脱乙酰酶活性。SIRT3在健康心脏中高水平表达，但在衰老或患病心脏中表达下调。实验证据表明，提高SIRT3水平或活性可改善多种心脏病理状况。SIRT3的主要脱乙酰化靶点是线粒体蛋白，其中大多数参与能量代谢。因此，SIRT3通过调节心脏能量代谢来改善心脏健康。在本综述中，我们讨论了SIRT3在生理和病理背景下调节心脏代谢中的重要作用。具体而言，我们总结了最近的进展，这些进展强调了SIRT3作为心脏代谢主要调节因子的关键作用。我们还全面介绍了所有已知的SIRT3激活剂，并阐述了它们改善各种心脏病理状况中能量异常的治疗潜力。
