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线粒体活性及动力学变化与衰老和肥胖中的新陈代谢的关系

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.

作者信息

López-Lluch Guillermo

机构信息

Universidad Pablo de Olavide, Dept. Fisiología, Anatomía y Biología Celular, Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto de Salud Carlos III, Carretera de Utrera km. 1, 41013 Sevilla, Spain.

出版信息

Mech Ageing Dev. 2017 Mar;162:108-121. doi: 10.1016/j.mad.2016.12.005. Epub 2016 Dec 16.

DOI:10.1016/j.mad.2016.12.005
PMID:27993601
Abstract

Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus.

摘要

线粒体在衰老和长寿过程中起着至关重要的作用。在衰老过程中,新陈代谢普遍失调,影响生物体中的分子、细胞和生理活动。线粒体功能障碍与衰老及年龄相关疾病有关,这表明它们在维持细胞内稳态方面的重要性。三种主要的营养传感器,即mTOR、AMPK和Sirtuins,参与线粒体生理的调控。这些营养传感器通过调节融合和裂变过程来控制线粒体生物发生、动态变化,并通过线粒体自噬和自噬来控制线粒体更新。除了参与融合的已知因子OPA1和线粒体融合蛋白,以及参与裂变的DRP1和FIS1外,诸如抑制素和 sestrins等新出现的因子在调节线粒体动态变化中也可发挥重要作用。线粒体还受到性激素的影响,而性激素在衰老过程中会发生剧烈变化。最近的文献表明,在脂肪组织生理学以及肌肉和肝脏等其他器官的脂肪积累过程中,营养传感器与线粒体稳态之间存在复杂的相互作用。在本文中,我们对线粒体稳态在衰老和年龄依赖性脂肪积累中的作用进行了综述。本综述强调了线粒体在衰老过程中脂肪积累以及肥胖、代谢综合征或2型糖尿病等相关疾病中的重要性。

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