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Endoplasmic reticulum stress-mediated mitochondrial dysfunction in aged hearts.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-07-19 , DOI: 10.1016/j.bbadis.2020.165899
Qun Chen 1 , Arun Samidurai 1 , Jeremy Thompson 1 , Ying Hu 1 , Anindita Das 1 , Belinda Willard 2 , Edward J Lesnefsky 3
Affiliation  

Aging impairs the mitochondrial electron transport chain (ETC), especially in interfibrillar mitochondria (IFM). Mitochondria are in close contact with the endoplasmic reticulum (ER). Induction of ER stress leads to ETC injury in adult heart mitochondria. We asked if ER stress contributes to the mitochondrial dysfunction during aging. Subsarcolemmal mitochondria (SSM) and IFM were isolated from 3, 18, and 24 mo. C57Bl/6 mouse hearts. ER stress progressively increased with age, especially in 24 mo. mice that manifest mitochondrial dysfunction. OXPHOS was decreased in 24 mo. IFM oxidizing complex I and complex IV substrates. Proteomic analysis showed that the content of multiple complex I subunits was decreased in IFM from 24 mo. hearts, but remained unchanged in in 18 mo. IFM without a decrease in OXPHOS. Feeding 24 mo. old mice with 4-phenylbutyrate (4-PBA) for two weeks attenuated the ER stress and improved mitochondrial function. These results indicate that ER stress contributes to the mitochondrial dysfunction in aged hearts. Attenuation of ER stress is a potential approach to improve mitochondrial function in aged hearts.



中文翻译:

内质网应激介导的老年心脏线粒体功能障碍。

衰老会损害线粒体电子传递链 (ETC),尤其是在原纤维间线粒体 (IFM) 中。线粒体与内质网(ER)密切接触。ER 应激的诱导导致成人心脏线粒体中的 ETC 损伤。我们询问内质网应激是否会导致衰老过程中的线粒体功能障碍。从 3、18 和 24 个月分离出肌膜下线粒体 (SSM) 和 IFM。C57Bl/6 小鼠心脏。ER 应力随着年龄的增长而逐渐增加,尤其是在 24 个月。表现出线粒体功能障碍的小鼠。OXPHOS 在 24 个月内下降。IFM 氧化复合物 I 和复合物 IV 底物。蛋白质组学分析显示IFM中多个复合物I亚基的含量从24个月开始下降。心,但在 18 个月内保持不变。IFM 没有减少 OXPHOS。喂食 24 个月。服用 4-苯基丁酸 (4-PBA) 两周的老年小鼠可减轻 ER 应激并改善线粒体功能。这些结果表明,ER 应激会导致老年心脏的线粒体功能障碍。减轻内质网应激是改善老年心脏线粒体功能的一种潜在方法。

更新日期:2020-07-30
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