Lee Yu Mi, Lee Duk Hee
Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.
Diabetes Metab J. 2019 Oct;43(5):568-577. doi: 10.4093/dmj.2019.0143.
Mitochondrial function is crucial for the maintenance of cellular homeostasis under physiological and stress conditions. Thus, chronic exposure to environmental chemicals that affect mitochondrial function can have harmful effects on humans. We argue that the concept of hormesis should be revisited to explain the non-linear responses to mitochondrial toxins at a low-dose range and develop practical methods to protect humans from the negative effects of mitochondrial toxins. Of the most concern to humans are lipophilic chemical mixtures and heavy metals, owing to their physical properties. Even though these chemicals tend to demonstrate no safe level in humans, a non-linear dose-response has been also observed. Stress response activation, i.e., hormesis, can explain this non-linearity. Recently, hormesis has reemerged as a unifying concept because diverse stressors can induce similar stress responses. Besides potentially harmful environmental chemicals, healthy lifestyle interventions such as exercise, calorie restriction (especially glucose), cognitive stimulation, and phytochemical intake also activate stress responses. This conceptual link can lead to the development of practical methods that counterbalance the harm of mitochondrial toxins. Unlike chemical hormesis with its safety issues, the activation of stress responses via lifestyle modification can be safely used to combat the negative effects of mitochondrial toxins.
线粒体功能对于在生理和应激条件下维持细胞内稳态至关重要。因此，长期接触影响线粒体功能的环境化学物质可能会对人类产生有害影响。我们认为，应该重新审视毒物兴奋效应的概念，以解释在低剂量范围内对线粒体毒素的非线性反应，并开发切实可行的方法来保护人类免受线粒体毒素的负面影响。由于其物理性质，亲脂性化学混合物和重金属是人类最关注的物质。尽管这些化学物质在人体中往往没有安全剂量，但也观察到了非线性剂量反应。应激反应激活，即毒物兴奋效应，可以解释这种非线性。最近，毒物兴奋效应作为一个统一的概念重新出现，因为多种应激源可以诱导相似的应激反应。除了潜在有害的环境化学物质外，健康的生活方式干预，如运动、热量限制（尤其是葡萄糖）、认知刺激和植物化学物质摄入，也会激活应激反应。这种概念上的联系可以导致开发出能够抵消线粒体毒素危害的实用方法。与存在安全问题的化学毒物兴奋效应不同，通过生活方式改变激活应激反应可以安全地用于对抗线粒体毒素的负面影响。
