Diabetes Metab J.  2019 Oct;43(5):568-577. 10.4093/dmj.2019.0143.

Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis

Affiliations
  • 1Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. lee_dh@knu.ac.kr
  • 2BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.

Abstract

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.

Keyword

Dementia; Diabetes mellitus, type 2; Environmental exposure; Environmental pollutants; Healthy lifestyle; Homeostasis; Hormesis; Mitochondria; Nonlinear dynamics; Organic chemicals

MeSH Terms

Dementia
Diabetes Mellitus, Type 2
Environmental Exposure
Environmental Pollutants
Homeostasis
Hormesis*
Humans
Life Style*
Metals, Heavy
Mitochondria
Nonlinear Dynamics
Organic Chemicals
Environmental Pollutants
Metals, Heavy
Organic Chemicals

Figure

  • Fig. 1 Comparison of three reactive oxygen species (ROS) dose-response curves. (A) Traditional linearity. (B) Biphasic hormetic curve I. (C) Biphasic hormetic curve II.

  • Fig. 2 Comparison between the low-dose range (zone A+B) and high dose range (zone C). Chronic exposure to low-dose chemical mixtures can be harmful (zone A), but the risk can flatten or decrease (zone B) through the activation of stress responses (i.e., hormesis). The traditional biphasic hormesis curve contrasts only a beneficial low-dose (zone B) with a harmful toxicity dose (zone C) but does not properly examine the negative effects in the sub-hormetic zone (zone A).

  • Fig. 3 Comparison between (A) transient exposure and (B) chronic exposure to low-dose mitochondrial toxins. Transient exposure can be overcome via the activation of stress responses in which mitochondrial toxins themselves play a role as stressors. However, chronic exposure can lead to the development of pathological conditions through chronic glutathione (GSH) depletion and other mitochondrial dysfunction. In this situation, the activation of stress responses using other stressors is needed to mitigate negative effects of chronic mitochondrial dysfunction. Among various stressors, exercise, calorie restriction (especially glucose), cognitive stimulation, and phytochemicals are examples of stressors that are considered acceptable to the public. ROS, reactive oxygen species.


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Diabetes Metab J. 2022;46(4):592-604.    doi: 10.4093/dmj.2021.0132.


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