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Review
. 2018 Nov 26;5(1):41.
doi: 10.1186/s40779-018-0187-0.

Potential therapy strategy: targeting mitochondrial dysfunction in sepsis

Affiliations
Review

Potential therapy strategy: targeting mitochondrial dysfunction in sepsis

"V体育2025版" Hui Zhang et al. Mil Med Res. .

V体育2025版 - Abstract

Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondria-targeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications. VSports手机版.

Keywords: Electron transfer chain; Mitochondria; Monitor; Sepsis; Therapy strategy. V体育安卓版.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

Figures (VSports最新版本)

Fig. 1
Fig. 1
Electron transport chain (ETC) components and its function. NADH and FADH2 are produced from the intermediary metabolism of glucose (carbohydrate), lipid (fat), and glutamine (protein); and they donate electrons to complex I (NADH-ubiquinone oxidoreductase) and complex II (succinate-ubiquinone oxidoreductase). These electrons are passed sequentially to coenzyme Q (or ubiquinone) to form CoQH2, and then transfers its electron to complex III (ubiquinol-cytochrome C oxidase reductase). Complex III transfers electrons to cytochrome C, which pass them to complex IV (cytochrome C oxidase or COX). At last complex IV donates an electron to O2 to produce H2O. The energy liberated by the flow of electrons is used by complexes I, III, and IV to pump protons (H+) out of the mitochondrial inner membrane (IM) into the intermembrane space. This proton gradient generates the mitochondrial membrane potential that is coupled to ATP (Adenosin triiphosphate) synthesis by complex V (ATPase) from ADP (adenosin diphosphate) and inorganic phosphate (Pi). OM. Outer membrane; NADH. Oxidized nicotinamide adenine dinucleotide; NAD+. Reduced nicotinamide adenine dinucleotide; FADH. Oxidized flavin adenine dinucleotide; FAD+. Reduced flavin adenine dinucleotide
Fig. 2
Fig. 2
Mitochondria dysfunction in sepsis. The electron transport chain (ETC) dysfunction results in extreme ROS production within mitochondria, which can lead to oxidative damage to mitochondria membrane, ETC activity and mtDNA. Mitochondrial membrane permeability transition results in release of cytochrome C (cyt C) into the cytosol, leading to apoptosis. Increased membrane permeability also makes the Ca2+ reflux into cytoplasm and a consequent disturbance that might further activate related signaling pathways. Mitochondrial ROS can also transport to cytoplasm and induce oxidative stress, following by oxidative stress signaling pathways activation which modulate various cellular functions. ROS released into extracellular space will further take harm to other cells and organs
Fig. 3
Fig. 3
Mitochondria targeted therapeutic strategies. The most potential therapy is TPP cation conjugated antioxidants including MitoQ, MitoE, MitoPrrioxidase, MitoTEMPO, and SKQ1, etc., which specifically accumulate into mitochondria and improve ETC function. Membrane stabilization inhibits ROS induced further membrane injury, protects mitochondria from swelling and rupture, and reduce molecule leakage that causes apoptosis and calcium disturbance in cytoplasm. The reagents include K-ATP channel blocker, 5-hydroxydecanoate (5-HD), etc. Mitochondrial biogenesis promotion by recombinant human mitochondrial transcription factor A (rhTFAM) reactivates mtDNA expressions, thereby enhancing mitochondrial protein expressions

References

    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315(8):801–810. doi: 10.1001/jama.2016.0287. - DOI - PMC - PubMed
    1. Arulkumaran N, Deutschman CS, Pinsky MR, Zuckerbraun B, Schumacker PT, Gomez H, et al. Mitochondrial function in sepsis. Shock. 2016;45(3):271–281. doi: 10.1097/SHK.0000000000000463. - DOI - PMC - PubMed
    1. Exline MC, Crouser ED. Mitochondrial mechanisms of sepsis-induced organ failure. Front Biosci. 2008;13(13):5030–5041. - PMC - PubMed
    1. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148(6):1145–1159. doi: 10.1016/j.cell.2012.02.035. - DOI - PMC - PubMed
    1. Lee I, Huttemann M. Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis. Biochem Biophys Acta. 2014;1842(9):1579–1586. - PMC - PubMed

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