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Diabetes Metab J : Diabetes & Metabolism Journal



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2 "Hormesis"
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Sulwon Lecture 2021
Basic Research
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Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim
Diabetes Metab J. 2022;46(3):402-413.   Published online May 25, 2022
  • 5,670 View
  • 241 Download
  • 9 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   ePub   
Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPRmt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.


Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
    Se Hee Min, Gil Myoung Kang, Jae Woo Park, Min-Seon Kim
    Yonsei Medical Journal.2024; 65(2): 55.     CrossRef
  • Roles of Myokines and Muscle-Derived Extracellular Vesicles in Musculoskeletal Deterioration under Disuse Conditions
    Jie Zhang, Yunfang Gao, Jiangwei Yan
    Metabolites.2024; 14(2): 88.     CrossRef
  • The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration
    Wacili Da, Quan Chen, Bin Shen
    Biological Research.2024;[Epub]     CrossRef
  • Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial b
    Lingfei Xu, Xihui Tang, Long Yang, Min Chang, Yuqing Xu, Qingsong Chen, Chen Lu, Su Liu, Jinhong Jiang
    Molecular Pain.2024;[Epub]     CrossRef
  • MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis
    Long Yang, Miaomiao Li, Yucheng Liu, Yang Bai, Tianyu Yin, Yangyang Chen, Jinhong Jiang, Su Liu
    Acta Biochimica et Biophysica Sinica.2024;[Epub]     CrossRef
  • Antifragility and antiinflammaging: Can they play a role for a healthy longevity?
    Fabiola Olivieri, Francesco Prattichizzo, Fabrizia Lattanzio, Anna Rita Bonfigli, Liana Spazzafumo
    Ageing Research Reviews.2023; 84: 101836.     CrossRef
  • MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
    Yuejun Zheng, Zilin Wei, Tianhui Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria
    Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv
    Mitochondrion.2023; 71: 76.     CrossRef
  • Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
    Byung Soo Kong, Changhan Lee, Young Min Cho
    Diabetes & Metabolism Journal.2023; 47(3): 315.     CrossRef
  • MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
    Remigiusz Domin, Michał Pytka, Mikołaj Żołyński, Jan Niziński, Marcin Rucinski, Przemysław Guzik, Jacek Zieliński, Marek Ruchała
    International Journal of Molecular Sciences.2023; 24(19): 14951.     CrossRef
  • Unique Properties of Apicomplexan Mitochondria
    Ian M. Lamb, Ijeoma C. Okoye, Michael W. Mather, Akhil B. Vaidya
    Annual Review of Microbiology.2023; 77(1): 541.     CrossRef
Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis
Yu-Mi Lee, Duk-Hee Lee
Diabetes Metab J. 2019;43(5):568-577.   Published online October 24, 2019
  • 6,211 View
  • 94 Download
  • 12 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   

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.


Citations to this article as recorded by  
  • Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress
    Sean M. Gettings, William Timbury, Anna Dmochowska, Riddhi Sharma, Rebecca McGonigle, Lewis E. MacKenzie, Guillaume Miquelard-Garnier, Nora Bourbia
    NanoImpact.2024; 34: 100508.     CrossRef
  • The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration
    Wacili Da, Quan Chen, Bin Shen
    Biological Research.2024;[Epub]     CrossRef
  • Rules of Heliogeomagnetics Diversely Coordinating Biological Rhythms and Promoting Human Health
    Kuniaki Otsuka, Germaine Cornelissen, Andi Weydahl, Denis Gubin, Larry A. Beaty, Masatoshi Murase
    Applied Sciences.2023; 13(2): 951.     CrossRef
  • Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
    Duk‐Hee Lee, In‐Kyu Lee
    Journal of Diabetes Investigation.2023; 14(4): 528.     CrossRef
  • Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm
    Giovanni Pagano, Antonios Apostolos Brouziotis, Daniel Lyons, Ivana Čarapar, Rahime Oral, Serkan Tez, Philippe J. Thomas, Franca Tommasi, Giovanni Libralato, Marco Guida, Marco Trifuoggi
    Bulletin of Environmental Contamination and Toxicology.2023;[Epub]     CrossRef
  • Mitochondria: It is all about energy
    Amaloha Casanova, Anne Wevers, Santiago Navarro-Ledesma, Leo Pruimboom
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • Type 2 Diabetes Induced by Changes in Proteomic Profiling of Zebrafish Chronically Exposed to a Mixture of Organochlorine Pesticides at Low Concentrations
    Yan Gao, Hyojin Lee, Sangkyu Lee, Ki-Tae Kim
    International Journal of Environmental Research and Public Health.2022; 19(9): 4991.     CrossRef
  • Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence
    Se-A Kim, Hoyul Lee, Sung-Mi Park, Mi-Jin Kim, Yu-Mi Lee, Young-Ran Yoon, Hyun-Kyung Lee, Hyo-Bang Moon, In-Kyu Lee, Duk-Hee Lee
    Diabetes & Metabolism Journal.2022; 46(4): 592.     CrossRef
  • Can Environmental Pollutants Be a Factor Linking Obesity and COVID-19?
    Duk-Hee Lee
    Journal of Korean Medical Science.2021;[Epub]     CrossRef
  • Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study
    Yu‐Mi Lee, Sun‐Hee Park, Duk‐Hee Lee
    Alzheimer's & Dementia.2020; 16(4): 696.     CrossRef
  • Lipophilic Environmental Chemical Mixtures Released During Weight‐Loss: The Need to Consider Dynamics
    Duk‐Hee Lee, David R Jacobs, Lars Lind, P. Monica Lind
    BioEssays.2020;[Epub]     CrossRef
  • Environmental toxicology and ecotoxicology: How clean is clean? Rethinking dose-response analysis
    Evgenios Agathokleous, Edward J. Calabrese
    Science of The Total Environment.2020; 746: 138769.     CrossRef

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