Journal of Bioenergetics and Biomembranes最新文献

Aim/introduction: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers.

Materials and methods: Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H₂DCFDA, respectively.

Results: Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2 mg/dL) compared to the untreated diabetic group (x̅=104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3 mg/dL) compared to the untreated diabetic rats (x̅=412.2 mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4 mg/dL vs. x̅=82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione.

Conclusion: Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.

Objective: Data in the GEO database (GSE63067) showed that G protein-coupled receptor 39 (GPR39) was down-regulated in tissues from patients with non-alcoholic fatty liver disease (NAFLD). It was intended to explore the mechanism of GPR39 in NAFLD.

Methods: HepG2 cells were treated with a mixture of oleic acid and palmitic acid (OA/PA) to mimic NAFLD cell models. The level of GPR39 and the functions of GPR39 on cellular oxidative stress, lipid accumulation, the SIRT1/Nrf2 signaling and mitochondrial dysfunction were assessed. To verify the mediation of the SIRT1 signaling pathway in GPR39 regulation, cells were subjected to SIRT1 inhibitor EX-527 treatment. Afterwards, the abovementioned aspects of cells were all determined.

Results: GPR39 presented a downward trend in response to OA/PA. GPR39 overexpression could suppress oxidative stress, lipid accumulation and activate the SIRT1/Nrf2 signaling. GPR39 overexpression likewise alleviated mitochondrial dysfunction, whereas EX-527 treatment disturbed the effects of GPR39 overexpression on these aspects.

Conclusion: The present study found that GPR39 reduced oxidative stress and maintained mitochondrial homeostasis in a cellular model of NAFLD, a process mediated by SIRT1/Nrf2 signaling.

Mitochondrial dysfunction plays a central role in Parkinson's disease (PD) and can be triggered by xenobiotics and mutations in mitochondrial quality control genes, such as the PINK1 gene. Caffeine has been proposed as a secondary treatment to relieve PD symptoms mainly by its antagonistic effects on adenosine receptors (ARs). Nonetheless, the potential protective effects of caffeine on mitochondrial dysfunction could be a strategy in PD treatment but need further investigation. In this study, we used high-resolution respirometry (HRR) to test caffeine's effects on mitochondrial dysfunction in PINK1^B9-null mutants of Drosophila melanogaster. PINK1 loss-of-function induced mitochondrial dysfunction in PINK1^B9-null flies observed by a decrease in O₂ flux related to oxidative phosphorylation (OXPHOS) and electron transfer system (ETS), respiratory control ratio (RCR) and ATP synthesis compared to control flies. Caffeine treatment improved OXPHOS and ETS in PINK^B9-null mutant flies, increasing the mitochondrial O₂ flux compared to untreated PINK^B9-null mutant flies. Moreover, caffeine treatment increased O₂ flux coupled to ATP synthesis and mitochondrial respiratory control ratio (RCR) in PINK 1^B9-null mutant flies. The effects of caffeine on respiratory parameters were abolished by rotenone co-treatment, suggesting that caffeine exerts its beneficial effects mainly by stimulating the mitochondrial complex I (CI). In conclusion, we demonstrate that caffeine may improve mitochondrial function by increasing mitochondrial OXPHOS and ETS respiration in the PD model using PINK1 loss-of-function mutant flies.

Background: Mitochondria are remarkably dynamic organelles encapsulated by bilayer membranes. The dynamic properties of mitochondria are critical for energy production.

Aims: The aim of our study is to investigate the global status and trends of mitochondrial dynamics research and predict popular topics and directions in the field.

Methods: Publications related to the studies of mitochondrial dynamics from 2002 to 2021 were retrieved from Web of Science database. A total of 4,576 publications were included. Bibliometric analysis was conducted by visualization of similarities viewer and GraphPadPrism 5 software.

Results: There is an increasing trend of mitochondrial dynamics research during the last 20 years. The cumulative number of publications about mitochondrial dynamics research followed the logistic growth model [Formula: see text]. The USA made the highest contributions to the global research. The journal Biochimica et Biophysica Acta (BBA)-Molecular Cell Research had the largest publication numbers. Case Western Reserve University is the most contributive institution. The main research orientation and funding agency were cell biology and HHS. All keywords related studies could be divided into three clusters: "Related disease research", "Mechanism research" and "Cell metabolism research".

Conclusions: Attention should be drawn to the latest popular research and more efforts will be put into mechanistic research, which may inspire new clinical treatments for the associated diseases.

Myocardial ischemia-reperfusion (I/R) injury is a major cause of poor hemodynamic reconstitution outcomes after myocardial infarction or circulatory arrest. Currently, the search for effective therapeutic agents and tools is a focus of research in the field of myocardial I/R injury. Resveratrol (Res) has been extensively studied in recent years because of its good cardiovascular therapeutic effects, but its specific mechanism of action has not been fully elucidated. Therefore, the aim of this study was to investigate the mechanism of interaction between myocardial I/R injury and Res in vitro and in vivo. In our in vivo study, we used PI/TUNEL staining and western blotting to detect relevant necroptotic key molecules such as RIP1, RIP3 and p-MLKL/MLKL to observe myocardial necroptosis. The extent of myocardial injury was determined using hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining as well as serum levels of CK-MB and LDH and echocardiography. In the in vitro study, cellular injury was assessed by CCK-8 and cell supernatant LDH levels. In addition, we used small interfering RNA (siRNA) transfection to knock down YAP, a key effector molecule of the Hippo pathway, to validate the molecular mechanism of action by which Res exerts myocardial protection. The localization of YAP in H9c2 cardiomyocytes was examined using immunofluorescence. Our data demonstrated that Res could ameliorate myocardial I/R-induced necroptosis by modulating the Hippo pathway, and that the beneficial effect of Res might be associated with nuclear translocation of the transcriptional regulator YAP.

The mitochondrial bc1 complex is a major source of mitochondrial superoxide. While bc1-generated superoxide plays a beneficial signaling role, excess production of superoxide lead to aging and degenerative diseases. The catalytic core of bc1 comprises three peptides -cytochrome b, Fe-S protein, and cytochrome c1. All three core peptides exhibit accelerated evolution in anthropoid primates. It has been suggested that the evolution of cytochrome b in anthropoids was driven by a pressure to reduce the production of superoxide. In humans, the bc1 core peptides exhibit anthropoid-specific substitutions that are clustered near functionally critical sites that may affect the production of superoxide. Here we compare the high-resolution structures of bovine, mouse, sheep and human bc1 to identify structural changes that are associated with human-specific substitutions. Several cytochrome b substitutions in humans alter its interactions with other subunits. Most significantly, there is a cluster of seven substitutions, in cytochrome b, the Fe-S protein, and cytochrome c1 that affect the interactions between these proteins at the tether arm of the Fe-S protein and may alter the rate of ubiquinone oxidation and the rate of superoxide production. Another cluster of substitutions near heme bH and the ubiquinone reduction site, Qi, may affect the rate of ubiquinone reduction and thus alter the rate of superoxide production. These results are compatible with the hypothesis that cytochrome b in humans (and other anthropoid primates) evolve to reduce the rate of production of superoxide thus enabling the exceptional longevity and exceptional cognitive ability of humans.

Exposure to the environmental pollutant lead (Pb) has been linked to Alzheimer's disease (AD), in which mitochondrial dysfunction is a pathological consequence of neuronal degeneration. The toxicity of Pb in combination with β-amyloid peptides (1-40) and (25-35) causes selective death in neuronal cells. However, the precise mechanism through which Pb induces Alzheimer's disease, particularly mitochondrial damage, is unknown. Changes in mitochondrial mass, membrane potential, mitochondrial complex activities, mitochondrial DNA and oxidative stress were examined in neuronal cells of human origin exposed to Pb and β-amyloid peptides (1-40) and (25-35) individually and in different combinations. The results showed depolarization of mitochondrial membrane potential, decrease in mitochondrial mass, ATP levels and mtDNA copy number in Pb and β-amyloid peptides (1-40) and (25-35) exposed cells. Also, significant reductions in the expression of mitochondrial electron transport chain (ETC) complex proteins (ATP5A, COXIV, UQCRC2, SDHB, NDUFS3), as well as down regulation of ETC complex gene expressions such as COXIV, ATP5F1 and NDUFS3 and antioxidant gene expressions like MnSOD and Gpx4 were observed in exposed cells. Furthermore, Pb and β-amyloid peptides exposure resulted in elevated mitochondrial malondialdehyde levels and a decrease in mitochondrial GSH levels. Our findings suggest that Pb toxicity could be one of the causative factors for the mitochondrial dysfunction and oxidative stress in Alzheimer's disease progression.

Bacillus subtilis is a Gram-positive bacterium with a respiratory chain embedded in the cytoplasmic membrane. The respiratory chain is bifurcated after menaquinol into a cytochrome b₆c + caa₃ branch and a branch with up to three quinol oxidases. The complexes that generate the proton gradient are b₆c, associated with caa₃ and aa₃ oxidase. The b₆c and caa₃ complexes form a supercomplex, and it is proposed to form respiratory strings in the membrane. There is still information missing about the quinol branch and if the primary oxidase quinol aa₃ is associated with the electron donor complexes. It is unclear whether succinate quinone reductase (SQR) can form associations with the quinol branch or the cytochrome branch. In this paper, we show the separation of an almost pure b₆c complex associated with cytochromes c₅₅₀ and c₅₅₁. We obtained a b₆c + caa₃ supercomplex of 600 kDa and SQR, aa₃, and NADH dehydrogenase by dodecyl maltoside solubilization and separation of the respiratory chain components by ionic exchange chromatography. We found that aa₃ does not associate with other complexes. SQR was associated with the b₆c complex in a mutant lacking aa₃. This association could facilitate electron transfer from SQR to menaquinone-7. The lack of associations between the abundant quinol oxidase aa₃ and other complexes is a feature we cannot explain yet.

Salinibacter ruber is an extremophilic bacterium able to grow in high-salts environments, such as saltern crystallizer ponds. This halophilic bacterium is red-pigmented due to the production of several carotenoids and their derivatives. Two of these pigment molecules, salinixanthin and retinal, are reported to be essential cofactors of the xanthorhodopsin, a light-driven proton pump unique to this bacterium. Here, we isolate and characterize an outer membrane porin-like protein that retains salinixanthin. The characterization by mass spectrometry identified an unknown protein whose structure, predicted by AlphaFold, consists of a 8 strands beta-barrel transmembrane organization typical of porins. The protein is found to be part of a functional network clearly involved in the outer membrane trafficking. Cryo-EM micrographs showed the shape and dimensions of a particle comparable with the ones of the predicted structure. Functional implications, with respect to the high representativity of this protein in the outer membrane fraction, are discussed considering its possible role in primary functions such as the nutrients uptake and the homeostatic balance. Finally, also a possible involvement in balancing the charge perturbation associated with the xanthorhodopsin and ATP synthase activities is considered.