Mitochondrial fusion, fission, and mitochondrial toxicity.
Mitochondrial fusion, fission, and mitochondrial toxicity.
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DOI：
10.1016/j.tox.2017.07.019
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发表时间：
2017-11-01
期刊：
影响因子：
4.5
通讯作者：
Luz AL
中科院分区：
文献类型：
--
作者：
Meyer JN;Leuthner TC;Luz AL
线粒体动力学由两组相反的过程调节：线粒体融合和分裂，线粒体生物发生和降解（包括线粒体自噬），以及细胞内转运等过程。这些过程维持线粒体稳态，调节线粒体的形式，体积和功能，并越来越多地被理解为细胞应激反应的关键组成部分。线粒体动力学根据发育阶段和年龄、细胞类型、环境因素和遗传背景而变化。事实上，许多线粒体稳态基因是人类疾病基因。新出现的证据表明，这些基因的缺陷往往对环境暴露敏感，但在某些情况下也可以保护。线粒体动力学的抑制也影响不可修复的线粒体DNA（mtDNA）损伤的消除和mtDNA突变的传递。我们简要地回顾了线粒体融合和裂变的重点的线粒体动力学过程的基础生物学，讨论了已知的和未知的关于这些过程如何应对化学和其他压力，并回顾了线粒体毒性和线粒体融合和裂变基因的遗传变异之间的相互作用的文献。最后，我们提出了未来研究的方向，包括阐明从低到高水平暴露，从急性到慢性暴露的全方位的有丝分裂动力学反应;详细检查不同细胞类型中有丝分裂动力学改变的生理后果;基于机制的有丝分裂毒性相互作用与有丝分裂动力学过程中个体间变异性的测试;并结合其他影响线粒体的环境变量，如饮食和运动。
Mitochondrial dynamics are regulated by two sets of opposed processes: mitochondrial fusion and fission, and mitochondrial biogenesis and degradation (including mitophagy), as well as processes such as intracellular transport. These processes maintain mitochondrial homeostasis, regulate mitochondrial form, volume and function, and are increasingly understood to be critical components of the cellular stress response. Mitochondrial dynamics vary based on developmental stage and age, cell type, environmental factors, and genetic background. Indeed, many mitochondrial homeostasis genes are human disease genes. Emerging evidence indicates that deficiencies in these genes often sensitize to environmental exposures, yet can also be protective under certain circumstances. Inhibition of mitochondrial dynamics also affects elimination of irreparable mitochondrial DNA (mtDNA) damage and transmission of mtDNA mutations. We briefly review the basic biology of mitodynamic processes with a focus on mitochondrial fusion and fission, discuss what is known and unknown regarding how these processes respond to chemical and other stressors, and review the literature on interactions between mitochondrial toxicity and genetic variation in mitochondrial fusion and fission genes. Finally, we suggest areas for future research, including elucidating the full range of mitodynamic responses from low to high-level exposures, and from acute to chronic exposures; detailed examination of the physiological consequences of mitodynamic alterations in different cell types; mechanism-based testing of mitotoxicant interactions with interindividual variability in mitodynamics processes; and incorporating other environmental variables that affect mitochondria, such as diet and exercise.
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