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Review

Mitochondria as a Source and a Target for Uremic Toxins

1
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia
2
V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia
3
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia
4
Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow 119991, Russia
5
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(12), 3094; https://doi.org/10.3390/ijms20123094
Received: 28 May 2019 / Revised: 19 June 2019 / Accepted: 21 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Bioactive and Uremic Toxins in Chronic Kidney Disease)
Elucidation of molecular and cellular mechanisms of the uremic syndrome is a very challenging task. More than 130 substances are now considered to be “uremic toxins” and represent a very diverse group of molecules. The toxicity of these molecules affects many cellular processes, and expectably, some of them are able to disrupt mitochondrial functioning. However, mitochondria can be the source of uremic toxins as well, as the mitochondrion can be the site of complete synthesis of the toxin, whereas in some scenarios only some enzymes of the pathway of toxin synthesis are localized here. In this review, we discuss the role of mitochondria as both the target and source of pathological processes and toxic compounds during uremia. Our analysis revealed about 30 toxins closely related to mitochondria. Moreover, since mitochondria are key regulators of cellular redox homeostasis, their functioning might directly affect the production of uremic toxins, especially those that are products of oxidation or peroxidation of cellular components, such as aldehydes, advanced glycation end-products, advanced lipoxidation end-products, and reactive carbonyl species. Additionally, as a number of metabolic products can be degraded in the mitochondria, mitochondrial dysfunction would therefore be expected to cause accumulation of such toxins in the organism. Alternatively, many uremic toxins (both made with the participation of mitochondria, and originated from other sources including exogenous) are damaging to mitochondrial components, especially respiratory complexes. As a result, a positive feedback loop emerges, leading to the amplification of the accumulation of uremic solutes. Therefore, uremia leads to the appearance of mitochondria-damaging compounds, and consecutive mitochondrial damage causes a further rise of uremic toxins, whose synthesis is associated with mitochondria. All this makes mitochondrion an important player in the pathogenesis of uremia and draws attention to the possibility of reducing the pathological consequences of uremia by protecting mitochondria and reducing their role in the production of uremic toxins. View Full-Text
Keywords: uremia; oxidative stress; mitochondria; kidney injury; toxins uremia; oxidative stress; mitochondria; kidney injury; toxins
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MDPI and ACS Style

Popkov, V.A.; Silachev, D.N.; Zalevsky, A.O.; Zorov, D.B.; Plotnikov, E.Y. Mitochondria as a Source and a Target for Uremic Toxins. Int. J. Mol. Sci. 2019, 20, 3094. https://doi.org/10.3390/ijms20123094

AMA Style

Popkov VA, Silachev DN, Zalevsky AO, Zorov DB, Plotnikov EY. Mitochondria as a Source and a Target for Uremic Toxins. International Journal of Molecular Sciences. 2019; 20(12):3094. https://doi.org/10.3390/ijms20123094

Chicago/Turabian Style

Popkov, Vasily A., Denis N. Silachev, Arthur O. Zalevsky, Dmitry B. Zorov, and Egor Y. Plotnikov. 2019. "Mitochondria as a Source and a Target for Uremic Toxins" International Journal of Molecular Sciences 20, no. 12: 3094. https://doi.org/10.3390/ijms20123094

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