Functional Mitochondria in Health and Disease.
Functional Mitochondria in Health and Disease.
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DOI：
10.3389/fendo.2017.00296
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发表时间：
2017
影响因子：
5.2
通讯作者：
Berridge MV
中科院分区：
文献类型：
--
作者：
Herst PM;Rowe MR;Carson GM;Berridge MV
快速调整细胞生物能量能力以满足快速变化的环境条件的能力是正常细胞功能和癌症进展所必需的。这种适应性反应的任何丧失都有可能损害细胞功能，使细胞更容易受到外部应激因素的影响，如氧化应激、辐射、化疗药物和缺氧。线粒体在生物能量和生物合成途径中起着至关重要的作用，可以快速调整以满足细胞的代谢需求。增加的需求通过线粒体生物发生和单个线粒体融合成动态网络来满足，而需求的减少导致通过分裂和有丝分裂去除多余的线粒体。核与线粒体之间的有效交流(有丝分裂-核串扰)，涉及不同线粒体应激信号的产生以及处理这些应激源的核应激反应途径，在大多数情况下维持生物能量平衡。然而，当线粒体DNA(MtDNA)突变累积和有丝分裂核串扰时，线粒体无法提供关键的功能输出。线粒体DNA突变与神经肌肉和神经退行性线粒体疾病以及糖尿病、心血管疾病、胃肠道疾病、皮肤疾病、衰老和癌症等复杂疾病有关。在某些情况下，会采取激烈的措施，如从供体细胞获取新的线粒体，以确保细胞存活。本文首先简要讨论线粒体的进化起源，并总结线粒体DNA突变是如何导致线粒体疾病和其他退行性疾病的。综述了线粒体产生的各种应激信号以及相应的核激活的应激反应途径等与核相关的信号串扰。我们还介绍和讨论了最近发现的调节身体新陈代谢的激素样丝裂多肽的一个小家族。在严重的线粒体应激条件下，线粒体被证明可以在细胞之间进行运输，用受损和故障的mtDNA取代细胞中的线粒体。了解细胞生物能量学和代谢适应的过程有可能产生新的知识，从而改进现代社会特征的许多代谢性、退化性和与年龄相关的炎症性疾病的治疗。
The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. Effective communication between nucleus and mitochondria (mito-nuclear cross talk), involving the generation of different mitochondrial stress signals as well as the nuclear stress response pathways to deal with these stressors, maintains bioenergetic homeostasis under most conditions. However, when mitochondrial DNA (mtDNA) mutations accumulate and mito-nuclear cross talk falters, mitochondria fail to deliver critical functional outputs. Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer. In some cases, drastic measures such as acquisition of new mitochondria from donor cells occurs to ensure cell survival. This review starts with a brief discussion of the evolutionary origin of mitochondria and summarizes how mutations in mtDNA lead to mitochondriopathies and other degenerative diseases. Mito-nuclear cross talk, including various stress signals generated by mitochondria and corresponding stress response pathways activated by the nucleus are summarized. We also introduce and discuss a small family of recently discovered hormone-like mitopeptides that modulate body metabolism. Under conditions of severe mitochondrial stress, mitochondria have been shown to traffic between cells, replacing mitochondria in cells with damaged and malfunctional mtDNA. Understanding the processes involved in cellular bioenergetics and metabolic adaptation has the potential to generate new knowledge that will lead to improved treatment of many of the metabolic, degenerative, and age-related inflammatory diseases that characterize modern societies.
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影响因子：
64.8
作者：
Alvarez-Dolado, M;Pardal, R;Alvarez-Buylla, A
通讯作者：
Alvarez-Buylla, A
影响因子：
5.2
作者：
Chen Y;Zhang H;Zhou HJ;Ji W;Min W
通讯作者：
Min W
影响因子：
2.8
作者：
Courtnay, Rupert;Ngo, Darleen C.;Karagiannis, Tom C.
通讯作者：
Karagiannis, Tom C.
影响因子：
3
作者：
de Souza, PL;Liauw, W;Howes, LG
通讯作者：
Howes, LG
影响因子：
50.5
作者：
Choueiri, TK;Mekhail, T;Bukowski, RM
通讯作者：
Bukowski, RM