Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China.
State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China.
J Cardiovasc Transl Res. 2024 Feb;17(1):104-120. doi: 10.1007/s12265-023-10382-w. Epub 2023 Apr 4.
Mitochondrial protein sequence similarity 3 gene family member A (FAM3A) plays important roles in the electron transfer chain, while its functions in the heart are still unknown. This study aims to explore the roles and mechanisms of FAM3A after myocardial infarction (MI). FAM3A-deficient (Fam3a) mice were implemented with MI injury and showed lower survival rates at 4 weeks as well as decreased cardiac systolic function. Isolated cardiomyocytes of Fam3a mice showed reduced basal, ATP-linked respiration and respiratory reserve compared to that of wild-type mice. Transmission electron microscopy studies showed Fam3a mice had a larger size and elevated density of mitochondria. FAM3A deficiency also induced elevated mitochondrial Ca, higher opening level of mPTP, lower mitochondrial membrane potential and elevated apoptotic rates. Further analyses demonstrated that mitochondrial dynamics protein Opa1 contributed to the effects of FAM3A in cardiomyocytes. Our study discloses the important roles of mitochondrial protein FAM3A in the heart.
线粒体蛋白序列相似性 3 基因家族成员 A（FAM3A）在电子传递链中发挥重要作用，但其在心脏中的功能尚不清楚。本研究旨在探讨 FAM3A 在心肌梗死（MI）后的作用和机制。FAM3A 缺失（Fam3a）小鼠进行 MI 损伤后，在 4 周时的存活率较低，并且心脏收缩功能下降。与野生型小鼠相比，Fam3a 小鼠的分离心肌细胞的基础、ATP 连接呼吸和呼吸储备减少。透射电子显微镜研究表明 Fam3a 小鼠的线粒体体积更大、密度更高。FAM3A 缺失还导致线粒体 Ca 升高、mPTP 开口水平升高、线粒体膜电位降低和凋亡率升高。进一步的分析表明，线粒体动力学蛋白 Opa1 有助于 FAM3A 在心肌细胞中的作用。我们的研究揭示了线粒体蛋白 FAM3A 在心脏中的重要作用。
