LncRNA LOC105378097 inhibits cardiac mitophagy in natural ageing mice

作者：Xin Liu, Xue Bai, Heng Liu, Yang Hong, Hao Cui, Lei Wang, Wanqing Xu, Limin Zhao, Xiaohan Li, Huimin Li, Xia Li, Hui Chen, Ziyu Meng, Han Lou, Henghui Xu, Yuan Lin, Zhimin Du, Philipp Kopylov, Baofeng Yang, Yong Zhang · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.908 · 被引用次数：22 · 研究领域：Autophagy in Disease and Therapy、Cancer-related molecular mechanisms research、Mitochondrial Function and Pathology

BACKGROUND: The development of heart ageing is the main cause of chronic disability, disease and death in the elderly. Ample evidence has established a pivotal role for significantly reduced mitophagy in the ageing heart. However, the underlying mechanisms of mitophagy deficiency in ageing heart are little known. The present study aimed to explore the underlying mechanisms of lncRNA LOC105378097 (Senescence-Mitophagy Associated LncRNA, lncR-SMAL) actions on mitophagy in the setting of heart ageing. METHODS: The expression of lncR-SMAL was measured in serum from different ages of human and heart from different ages of mice through a quantitative real-time polymerase chain reaction. The effects of lncR-SMAL on heart function of mice were assessed by echocardiography and pressure-volume measurements system. Cardiac senescence was evaluated by hematoxylin-eosin staining, senescence-associated β-galactosidase staining, flow cytometry and western blot analysis of expression of ageing related markes p53 and p21. Cardiomyocyte mitophagy was assessed by western blot, mRFP-GFP-LC3 adenovirus particles transfection and mito-Keima staining. Interaction between lncR-SMAL and Parkin was validated through molecular docking, RNA immunoprecipitation (RIP) and RNA pull-down assay. Ubiquitination assay was performed to explore the molecular mechanism of Parkin inhibition. The effects of lncR-SMAL on mitochondrial function were investigated through electron microscopic examination, JC-1 staining...