Greenwell Amanda A, Tabatabaei Dakhili Seyed Amirhossein, Ussher John R
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.
Front Cardiovasc Med. 2022 Aug 10;9:981972. doi: 10.3389/fcvm.2022.981972. eCollection 2022.
Barth Syndrome (BTHS) is a rare X-linked mitochondrial disorder due to mutations in the gene , which leads to immature cardiolipin (CL) remodeling and is characterized by the development of cardiomyopathy. The immature CL remodeling in BTHS results in electron transport chain respiratory defects and destabilization of supercomplexes, thereby impairing ATP production. Thus, BTHS-related cardiomyopathy appears to share metabolic characteristics of the failing heart being an "engine out of fuel." As CL associates with numerous mitochondrial enzymes involved in ATP production, BTHS is also characterized by several defects in intermediary energy metabolism. Herein we will describe the primary disturbances in intermediary energy metabolism relating to the heart's major fuel sources, fatty acids, carbohydrates, ketones, and amino acids. In addition, we will interrogate whether these disturbances represent potential metabolic targets for alleviating BTHS-related cardiomyopathy.
巴斯综合征（BTHS）是一种罕见的X连锁线粒体疾病，由该基因突变引起，导致心磷脂（CL）重塑不成熟，并以心肌病的发展为特征。BTHS中不成熟的CL重塑导致电子传递链呼吸缺陷和超复合物不稳定，从而损害ATP生成。因此，BTHS相关的心肌病似乎具有衰竭心脏“燃料耗尽”的代谢特征。由于CL与许多参与ATP生成的线粒体酶相关联，BTHS还具有中间能量代谢的几个缺陷。在此，我们将描述与心脏主要燃料来源（脂肪酸、碳水化合物、酮和氨基酸）相关的中间能量代谢的主要紊乱。此外，我们将探讨这些紊乱是否代表缓解BTHS相关心肌病的潜在代谢靶点。
