Öz
Hormesis is a process in which exposure to a low dose of a potentially harmful stressor promotes adaptive changes that enable the cell to better tolerate subsequent stress. Mitohormesis is a term used to describe a biological protective response in which the induction of a reduced amount of mitochondrial stress leads to an increase in health and vitality within a cell, tissue or organism. The mitochondrial stress response, activated by a potentially damaging stimulus, requires coordinated communication with the nucleus, known as mitonuclear communication. This communication, caused by the hormetic response in mitochondria, occurs through various signals such as reactive oxygen species (ROS), mitochondrial metabolites, proteotoxic signals, and the release of mitokines. In this paradigm, mild mitochondrial stress triggered by any of a variety of stimuli results in a broad and diverse cytosolic and nuclear response. Although multiple mediators and stress signals have been proposed to activate this protective mechanism, the beneficial consequences of mitohormesis are most likely due to an increase in mitochondrial ROS. Activation of the mitohormetic response has been reported to prolong lifespan in different animal models from worms to mammals. In addition, mitohormesis contributes to the health of the organism, especially by improving the metabolism and immune system.
Anahtar Kelimeler
Kaynakça
- 1. Bárcena C, Mayoral P, Quirós PM. Mitohormesis, an Antiaging Paradigm. Int Rev Cell Mol Biol. 2018; 340: 35-77. doi:10.1016/bs.ircmb.2018.05.002.
- 2. Tapia PC. Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality. Med Hypotheses. 2006; 66(4): 832-843. doi:10.1016/j.mehy.2005.09.009.
- 3. Yun J, Finkel T. Mitohormesis. Cell Metab. 2014; 19(5): 757-766. doi:10.1016/j.cmet.2014.01.011.
- 4. Quirós PM, Mottis A, Auwerx J. Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol. 2016; 17(4): 213-226. doi:10.1038/nrm.2016.23.
- 5. Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab. 2012; 23(9): 459-466. doi:10.1016/j.tem.2012.06.006.
- 6. Arnould T, Michel S, Renard P. Mitochondria Retrograde Signaling and the UPR mt: Where Are We in Mammals?. Int J Mol Sci. 2015; 16(8): 18224-18251. Published 2015 Aug 6. doi:10.3390/ijms160818224.
- 7. Guha M, Avadhani NG. Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion. 2013; 13(6): 577-591. doi:10.1016/j.mito.2013.08.007.
- 8. Ristow M, Schmeisser K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response. 2014; 12(2): 288-341. Published 2014 Jan 31. doi:10.2203/dose-response.13-035.Ristow.
- 9. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3): 298-300. doi:10.1093/geronj/11.3.298.
- 10. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009; 417(1): 1-13. doi:10.1042/BJ20081386.
- 11. Powers SK, Hogan MC. Exercise and oxidative stress. J Physiol. 2016; 594(18): 5079-5080. doi:10.1113/JP272255.
- 12. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007; 6(4): 280-293. doi:10.1016/j.cmet.2007.08.011.
- 13. Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 2010; 8(12): e1000556. Published 2010 Dec 7. doi:10.1371/journal.pbio.1000556.
- 14. Zarse K, Schmeisser S, Groth M, et al. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab. 2012; 15(4): 451-465. doi:10.1016/j.cmet.2012.02.013.
- 15. Ristow M, Schmeisser K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response. 2014; 12(2): 288-341. Published 2014 Jan 31. doi:10.2203/dose-response.13-035.
- 16. Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(5): 1066-1077. doi:10.1016/j.bbadis.2016.11.010.
- 17. Palmeira CM, Teodoro JS, Amorim JA, Steegborn C, Sinclair DA, Rolo AP. Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins. Free Radic Biol Med. 2019; 141: 483-491. doi:10.1016/j.freeradbiomed.2019.07.017.
- 18. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012; 13(9): 566-578. doi:10.1038/nrm3412.
- 19. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018; 19(2): 121-135. doi:10.1038/nrm.2017.95.
- 20. Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011; 331(6016): 456-461. doi:10.1126/science.1196371.
- 21. Toyama EQ, Herzig S, Courchet J, et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science. 2016; 351(6270): 275-281. doi:10.1126/science.aab4138.
- 22. Baker BM, Nargund AM, Sun T, Haynes CM. Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2. PLoS Genet. 2012; 8(6): e1002760. doi:10.1371/journal.pgen.1002760.
- 23. Wrobel L, Topf U, Bragoszewski P, et al. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature. 2015; 524(7566): 485-488. doi:10.1038/nature14951.
- 24. Melber A, Haynes CM. UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication. Cell Res. 2018; 28(3): 281-295. doi:10.1038/cr.2018.16.
- 25. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ. A mitochondrial specific stress response in mammalian cells. EMBO J. 2002; 21(17): 4411-4419. doi:10.1093/emboj/cdf445.
- 26. Shpilka T, Haynes CM. The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat Rev Mol Cell Biol. 2018; 19(2): 109-120. doi:10.1038/nrm.2017.110.
- 27. Tran HC, Van Aken O. Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators. Mitochondrion. 2020; 53: 166-177. doi:10.1016/j.mito.2020.05.009.
- 28. Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011; 144(1): 79-91. doi:10.1016/j.cell.2010.12.016.
- 29. Merry TL, Chan A, Woodhead JST, et al. Mitochondrial-derived peptides in energy metabolism. Am J Physiol Endocrinol Metab. 2020; 319(4): E659-E666. doi:10.1152/ajpendo.00249.2020.
- 30. Klaus S, Igual Gil C, Ost M. Regulation of diurnal energy balance by mitokines. Cell Mol Life Sci. 2021; 78(7): 3369-3384. doi:10.1007/s00018-020-03748-9.
Öz
Hormesis, düşük dozda potansiyel olarak zararlı bir stres etkenine maruz kalmanın, hücrenin sonraki stresi daha iyi tolere etmesini sağlayan adaptif değişiklikleri teşvik ettiği bir süreçtir. Mitohormesis ise, azaltılmış miktarda mitokondriyal stresin indüklenmesinin bir hücre, doku veya organizma içinde sağlık ve canlılıkta bir artışa yol açtığı biyolojik koruyucu bir yanıtı tanımlamak için kullanılan bir terim olarak karışımıza çıkmaktadır. Potansiyel olarak zarar verici bir uyaran tarafından aktive edilen mitokondriyal stres yanıtı, mitonükleer iletişim olarak bilinen çekirdek ile koordineli bir iletişim gerektirir. Mitokondrideki hormetik yanıtın neden olduğu bu iletişim, reaktif oksijen türleri (ROS), mitokondriyal metabolitler, proteotoksik sinyaller ve mitokinlerin salınımı gibi çeşitli sinyaller aracılığıyla meydana gelir. Bu paradigmada, çeşitli uyaranlardan herhangi biri tarafından tetiklenen hafif mitokondriyal stres, geniş ve çeşitli bir sitozolik ve nükleer tepki ile sonuçlanır. Bu koruyucu mekanizmayı aktive etmek için çoklu aracılar ve stres sinyalleri önerilmiş olsa da, mitohormesisin faydalı sonuçları büyük olasılıkla mitokondriyal ROS'taki bir artıştan dolayı meydana gelmektedir. Mitohormetik yanıtın aktive edilmesinin solucanlardan memelilere kadar farklı hayvan modellerinde yaşam süresini uzattığı belirtilmiştir. Ayrıca mitohormesis, özellikle metabolizmayı ve bağışıklık sistemini geliştirerek organizmanın sağlığını da katkıda bulunmaktadır.
Anahtar Kelimeler
Kaynakça
- 1. Bárcena C, Mayoral P, Quirós PM. Mitohormesis, an Antiaging Paradigm. Int Rev Cell Mol Biol. 2018; 340: 35-77. doi:10.1016/bs.ircmb.2018.05.002.
- 2. Tapia PC. Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality. Med Hypotheses. 2006; 66(4): 832-843. doi:10.1016/j.mehy.2005.09.009.
- 3. Yun J, Finkel T. Mitohormesis. Cell Metab. 2014; 19(5): 757-766. doi:10.1016/j.cmet.2014.01.011.
- 4. Quirós PM, Mottis A, Auwerx J. Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol. 2016; 17(4): 213-226. doi:10.1038/nrm.2016.23.
- 5. Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab. 2012; 23(9): 459-466. doi:10.1016/j.tem.2012.06.006.
- 6. Arnould T, Michel S, Renard P. Mitochondria Retrograde Signaling and the UPR mt: Where Are We in Mammals?. Int J Mol Sci. 2015; 16(8): 18224-18251. Published 2015 Aug 6. doi:10.3390/ijms160818224.
- 7. Guha M, Avadhani NG. Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion. 2013; 13(6): 577-591. doi:10.1016/j.mito.2013.08.007.
- 8. Ristow M, Schmeisser K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response. 2014; 12(2): 288-341. Published 2014 Jan 31. doi:10.2203/dose-response.13-035.Ristow.
- 9. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3): 298-300. doi:10.1093/geronj/11.3.298.
- 10. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009; 417(1): 1-13. doi:10.1042/BJ20081386.
- 11. Powers SK, Hogan MC. Exercise and oxidative stress. J Physiol. 2016; 594(18): 5079-5080. doi:10.1113/JP272255.
- 12. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007; 6(4): 280-293. doi:10.1016/j.cmet.2007.08.011.
- 13. Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 2010; 8(12): e1000556. Published 2010 Dec 7. doi:10.1371/journal.pbio.1000556.
- 14. Zarse K, Schmeisser S, Groth M, et al. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab. 2012; 15(4): 451-465. doi:10.1016/j.cmet.2012.02.013.
- 15. Ristow M, Schmeisser K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response. 2014; 12(2): 288-341. Published 2014 Jan 31. doi:10.2203/dose-response.13-035.
- 16. Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(5): 1066-1077. doi:10.1016/j.bbadis.2016.11.010.
- 17. Palmeira CM, Teodoro JS, Amorim JA, Steegborn C, Sinclair DA, Rolo AP. Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins. Free Radic Biol Med. 2019; 141: 483-491. doi:10.1016/j.freeradbiomed.2019.07.017.
- 18. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012; 13(9): 566-578. doi:10.1038/nrm3412.
- 19. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018; 19(2): 121-135. doi:10.1038/nrm.2017.95.
- 20. Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011; 331(6016): 456-461. doi:10.1126/science.1196371.
- 21. Toyama EQ, Herzig S, Courchet J, et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science. 2016; 351(6270): 275-281. doi:10.1126/science.aab4138.
- 22. Baker BM, Nargund AM, Sun T, Haynes CM. Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2. PLoS Genet. 2012; 8(6): e1002760. doi:10.1371/journal.pgen.1002760.
- 23. Wrobel L, Topf U, Bragoszewski P, et al. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature. 2015; 524(7566): 485-488. doi:10.1038/nature14951.
- 24. Melber A, Haynes CM. UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication. Cell Res. 2018; 28(3): 281-295. doi:10.1038/cr.2018.16.
- 25. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ. A mitochondrial specific stress response in mammalian cells. EMBO J. 2002; 21(17): 4411-4419. doi:10.1093/emboj/cdf445.
- 26. Shpilka T, Haynes CM. The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat Rev Mol Cell Biol. 2018; 19(2): 109-120. doi:10.1038/nrm.2017.110.
- 27. Tran HC, Van Aken O. Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators. Mitochondrion. 2020; 53: 166-177. doi:10.1016/j.mito.2020.05.009.
- 28. Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011; 144(1): 79-91. doi:10.1016/j.cell.2010.12.016.
- 29. Merry TL, Chan A, Woodhead JST, et al. Mitochondrial-derived peptides in energy metabolism. Am J Physiol Endocrinol Metab. 2020; 319(4): E659-E666. doi:10.1152/ajpendo.00249.2020.
- 30. Klaus S, Igual Gil C, Ost M. Regulation of diurnal energy balance by mitokines. Cell Mol Life Sci. 2021; 78(7): 3369-3384. doi:10.1007/s00018-020-03748-9.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Derlemeler |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Aralık 2022 |
| Gönderilme Tarihi | 4 Kasım 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 1 Sayı: 1 |
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