scholarly journals Supplementation of T3Recovers Hypothyroid Rat Liver Cells from Oxidatively Damaged Inner Mitochondrial Membrane Leading to Apoptosis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Sutapa Mukherjee ◽  
Luna Samanta ◽  
Anita Roy ◽  
Shravani Bhanja ◽  
Gagan B. N. Chainy
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Membrane ◽  
Membrane Lipids ◽  
Antioxidant Defenses ◽  
Hepatocyte Apoptosis ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Oxidative Stress ◽  
Rat Liver Cells ◽  
Matrix Fraction ◽  
Complex I Activity

Hypothyroidism is a growing medical concern. There are conflicting reports regarding the mechanism of oxidative stress in hypothyroidism. Mitochondrial oxidative stress is pivotal to thyroid dysfunction. The present study aimed to delineate the effects of hepatic inner mitochondrial membrane dysfunction as a consequence of 6-n-propyl-2-thiouracil-induced hypothyroidism in rats. Increased oxidative stress predominance in the submitochondrial particles (SMP) and altered antioxidant defenses in the mitochondrial matrix fraction correlated with hepatocyte apoptosis. In order to check whether the effects caused by hypothyroidism are reversed by T3, the above parameters were evaluated in a subset of T3-treated hypothyroid rats. Complex I activity was inhibited in hypothyroid SMP, whereas T3supplementation upregulated electron transport chain complexes. Higher mitochondrial H2O2levels in hypothyroidism due to reduced matrix GPx activity culminated in severe oxidative damage to membrane lipids. SMP and matrix proteins were stabilised in hypothyroidism but exhibited increased carbonylation after T3administration. Glutathione content was higher in both. Hepatocyte apoptosis was evident in hypothyroid liver sections; T3administration, on the other hand, exerted antiapoptotic and proproliferative effects. Hence, thyroid hormone level critically regulates functional integrity of hepatic mitochondria; hypothyroidism injures mitochondrial membrane lipids leading to hepatocyte apoptosis, which is substantially recovered upon T3supplementation.

scholarly journals The H+ Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 197
Author(s):  
Joseph A. Bonanno ◽  
Raji Shyam ◽  
Moonjung Choi ◽  
Diego G. Ogando
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Membrane ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Oxidative Stress ◽  
Antioxidant Genes ◽  
Knock Out ◽  
Bicarbonate Transporter ◽  
Mitochondrial Superoxide ◽  
Transporter Family

Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes. Outside of the corneal endothelium, SLC4A11’s function has been demonstrated in cochlear fibrocytes, salivary glands, and kidneys, but is largely unexplored overall. Increased SLC4A11 expression is a component of some “glutamine-addicted” cancers, and is possibly linked to cells and tissues that rely on glutamine catabolism.

scholarly journals Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1605
Author(s):  
Carlos Fernandes ◽  
Afonso J. C. Videira ◽  
Caroline D. Veloso ◽  
Sofia Benfeito ◽  
Pedro Soares ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Mitochondrial Membrane ◽  
Hepatic Cell ◽  
Therapeutic Application ◽  
Extracellular Acidification ◽  
Mitochondrial Oxidative Stress ◽  
Drug Candidates ◽  
Cellular Oxygen ◽  
Hepatic Cell Lines

Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100–1000× less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.

scholarly journals A ferredoxin bridge connects the two arms of plant mitochondrial complex I

2020 ◽  
Author(s):  
Niklas Klusch ◽  
Jennifer Senkler ◽  
Özkan Yildiz ◽  
Werner Kühlbrandt ◽  
Hans-Peter Braun
Keyword(s):  
Arabidopsis Thaliana ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inner Mitochondrial Membrane ◽  
Main Site ◽  
The Matrix ◽  
Quinol Binding ◽  
Complex I Activity

SUMMARYMitochondrial complex I is the main site for electron transfer to the respiratory chain and generates much of the proton gradient across the inner mitochondrial membrane. It is composed of two arms, which form a conserved L-shape. We report the structures of the intact, 47-subunit mitochondrial complex I from Arabidopsis thaliana and from the green alga Polytomella sp. at 3.2 and 3.3 Å resolution. In both, a heterotrimeric γ-carbonic anhydrase domain is attached to the membrane arm on the matrix side. Two states are resolved in A. thaliana complex I, with different angles between the two arms and different conformations of the ND1 loop near the quinol binding site. The angle appears to depend on a bridge domain, which links the peripheral arm to the membrane arm and includes an unusual ferredoxin. We suggest that the bridge domain regulates complex I activity.One sentence summaryThe activity of complex I depends on the angel between its two arms, which, in plants, is adjusted by a protein bridge that includes an unusual ferredoxin.The authors responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) are: Hans-Peter Braun ([email protected]) and Werner Kühlbrandt ([email protected]).

scholarly journals Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism

Hepatology ◽  
2002 ◽  
Vol 35 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Juan B. Miñana ◽  
Luis Gómez-Cambronero ◽  
Ana Lloret ◽  
Federico V. Pallardó ◽  
Juan Del Olmo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Alcoholism ◽  
Hepatocyte Apoptosis ◽  
Mitochondrial Oxidative Stress ◽  
Cd95 Ligand ◽  
Dual Mechanism

Mitochondrial oxidative stress-induced hepatocyte apoptosis reflects increased molybdenum intake in caprine

2015 ◽  
Vol 170 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Yu Zhuang ◽  
Ping Liu ◽  
Liqi Wang ◽  
Junrong Luo ◽  
Caiying Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocyte Apoptosis ◽  
Mitochondrial Oxidative Stress

scholarly journals The Role of Mitochondria in Liver Ischemia-Reperfusion Injury: From Aspects of Mitochondrial Oxidative Stress, Mitochondrial Fission, Mitochondrial Membrane Permeable Transport Pore Formation, Mitophagy, and Mitochondria-Related Protective Measures

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Haifeng Zhang ◽  
Qi Yan ◽  
Xuan Wang ◽  
Xin Chen ◽  
Ying Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Mitochondrial Membrane ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fusion ◽  
Protective Measures ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Structure

Ischemia-reperfusion injury (IRI) has indeed been shown as a main complication of hepatectomy, liver transplantation, trauma, and hypovolemic shock. A large number of studies have confirmed that microvascular and parenchymal damage is mainly caused by reactive oxygen species (ROS), which is considered to be a major risk factor for IRI. Under normal conditions, ROS as a kind of by-product of cellular metabolism can be controlled at normal levels. However, when IRI occurs, mitochondrial oxidative phosphorylation is inhibited. In addition, oxidative respiratory chain damage leads to massive consumption of adenosine triphosphate (ATP) and large amounts of ROS. Additionally, mitochondrial dysfunction is involved in various organs and tissues in IRI. On the one hand, excessive free radicals induce mitochondrial damage, for instance, mitochondrial structure, number, function, and energy metabolism. On the other hand, the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. According to the formation mechanism of IRI, various substances have been discovered or synthesized for specific targets and cell signaling pathways to inhibit or slow the damage of liver IRI to the body. Here, based on the development of this field, this review describes the role of mitochondria in liver IRI, from aspects of mitochondrial oxidative stress, mitochondrial fusion and fission, mPTP formation, and corresponding protective measures. Therefore, it may provide references for future clinical treatment and research.

scholarly journals Cobalt Chloride Alters Mitochondrial Function in a Dose Dependent Manner

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Pham Thi Bich ◽  
Vu Thi Thu
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Cobalt Chloride ◽  
Dose Dependence ◽  
Cell Counting ◽  
Dependent Manner ◽  
Mitochondrial Oxidative Stress ◽  
H9c2 Cardiomyocytes ◽  
Dose Dependent

Aim: This study was carried to evaluates of Cobalt chloride (CoCl2) on cardiac mitochondrial function. Methods: H9C2 cardiomyocytes were cultured in medium containing different concentrations of CoCl2. Cell viability, cardiolipin content, mitochondrial function, and mitochondrial oxidative stress were assessed by using Cell Counting Kit-8 and suitable fluorescence kits. Results: The obtained data showed that CoCl2 (200÷400 µM) induced cell death and decreased mitochondrial function of H9C2 cardiomyocytes in dose dependence. Especially, CoCl2 at dose of 300 µM significantly altered values of mitochondrial membrane potential, H2O2 and O2- to 63.79±2.15%, 145.81±5.83% and 143.10±3.07% (of 100% control), respectively. Conclusion: CoCl2 strongly induced cardiomyocyte death via altering mitochondrial function in a dose-dependent manner.

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