The role of mitochondria dysfunction and hepatic senescence in NAFLD development and progression
The role of mitochondria dysfunction and hepatic senescence in NAFLD development and progression
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DOI：
10.1016/j.biopha.2021.112041
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发表时间：
2021-08-16
影响因子：
7.5
通讯作者：
Orekhov, Alexander N.
中科院分区：
文献类型：
--
作者：
Dabravolski, Siarhei A.;Bezsonov, Evgeny E.;Orekhov, Alexander N.
衰老是几种代谢紊乱和慢性炎症性疾病的关键因素。最近的数据证明肝细胞衰老参与了非酒精性脂肪性肝病(NAFLD)的发生。线粒体作为机体的主要能量和产生ROS的细胞器，在加速衰老和疾病发展中起着核心作用。本文就线粒体钙稳态、NAD+/NADH比值、UPRmt(线粒体未折叠蛋白反应)、磷脂和脂肪酸氧化在肝脏衰老、寿命和NAFLD疾病易感性中的作用作一综述。此外，还讨论了线粒体和核突变在寿命调节和NAFLD发展中的作用。虽然核和线粒体DNA突变和单核苷酸多态(SNPs)可作为NAFLD有效的诊断标志和治疗靶点，但高龄应被视为NAFLD发生的独立危险因素。
Senescence is a crucial player in several metabolic disorders and chronic inflammatory diseases. Recent data prove the involvement of hepatocyte senescence in the development of NAFLD (non-alcoholic fatty liver disease). As the main energy and ROS (reactive oxygen species) producing organelle, mitochondria play the central role in accelerated senescence and diseases development. In this review, we focus on the role of regulation of mitochondrial Ca2+ homeostasis, NAD+/NADH ratio, UPRmt (mitochondrial unfolded protein response), phospholipids and fatty acid oxidation in hepatic senescence, lifespan and NAFLD disease susceptibility. Additionally, the involvement of mitochondrial and nuclear mutations in lifespan-modulation and NAFLD development is discussed. While nuclear and mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) can be used as effective diagnostic markers and targets for treatments, advanced age should be considered as an independent risk factor for NAFLD development.