Mitochondrial Dysfunction as a Hallmark of Environmental Injury
Abstract
:1. Introduction
2. Mitochondria as Crucial Organelles: From Healthy Metabolic Homeostasis to Critical Dysfunction
3. Mitochondrial Dysfunction upon Exposure to Environmental Pollutants: Multiple Mechanisms of Toxicity
4. AhR as a Crucial Player in Environmental Pollutant-Induced Mitochondrial Dysfunction
5. Concluding Remarks Related to Mitotoxicity and Risk Assessment
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Key Features of the Mitochondria | Consequences Regarding the Exposure to Xenobiotics |
---|---|
Mitochondria are complex organelles whose functions are governed by multiple and diverse proteins | As a result, a wide variety of xenobiotics can target the mitochondria such as polycyclic aromatic hydrocarbons, pesticides (including rotenone, pyrethroids, atrazine), metals (cadmium). |
Mitochondria are involved in the production of ATP which is coupled with the activity of the respiratory chain | Both processes (ATP production and respiration) are governed by complexes of the inner membrane which are targeted by natural and foreign compounds. Disruption of the respiratory chain can lead to the misuse of O2 and production of reactive oxygen species. It can also promote the Warburg Effect. |
Mitochondria regulate multiple cellular processes including cell proliferation, differentiation, apoptosis and mitophagy | Exposure to xenobiotics targeting the mitochondria can lead to disruption of such processes, leading to various outcomes (increased apoptosis and neurodegeneration; increased survival in cancer). |
Mitochondria crosstalk with epigenetics by regulating the levels of NAD+, S-adenosylmethionine, α-ketoglutarate, succinate and fumarate which impact epigenetic marks. | Several pollutants impact epigenetic marks through the deregulation of mitochondria-related metabolites and/or co-factors production, such as DDE, hexachlorobenzene, tributyltin, bisphenol A, phthalates or organochlorines |
Mitochondria contain transcriptional factors that regulate some of the functions mentioned earlier. | Binding of ligands to such transcriptional factors may lead to relocalization of these proteins to mitochondria and alteration of their properties (i.e., AhR and the Seveso dioxin) due for example to increased ROS production |
Some pollutants are non-persistent while other are persistent (with a long-half life in the body) | The nature of each xenobiotic is crucial to determine their long-term effects on the mitochondria: endogenous ligands or low doses-exogenous ligands can then be opposed to persistent exogenous ligands regarding the potential health outcomes they would induce |
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Duarte-Hospital, C.; Tête, A.; Brial, F.; Benoit, L.; Koual, M.; Tomkiewicz, C.; Kim, M.J.; Blanc, E.B.; Coumoul, X.; Bortoli, S. Mitochondrial Dysfunction as a Hallmark of Environmental Injury. Cells 2022, 11, 110. https://doi.org/10.3390/cells11010110
Duarte-Hospital C, Tête A, Brial F, Benoit L, Koual M, Tomkiewicz C, Kim MJ, Blanc EB, Coumoul X, Bortoli S. Mitochondrial Dysfunction as a Hallmark of Environmental Injury. Cells. 2022; 11(1):110. https://doi.org/10.3390/cells11010110
Chicago/Turabian StyleDuarte-Hospital, Carolina, Arnaud Tête, François Brial, Louise Benoit, Meriem Koual, Céline Tomkiewicz, Min Ji Kim, Etienne B. Blanc, Xavier Coumoul, and Sylvie Bortoli. 2022. "Mitochondrial Dysfunction as a Hallmark of Environmental Injury" Cells 11, no. 1: 110. https://doi.org/10.3390/cells11010110
APA StyleDuarte-Hospital, C., Tête, A., Brial, F., Benoit, L., Koual, M., Tomkiewicz, C., Kim, M. J., Blanc, E. B., Coumoul, X., & Bortoli, S. (2022). Mitochondrial Dysfunction as a Hallmark of Environmental Injury. Cells, 11(1), 110. https://doi.org/10.3390/cells11010110