Adenosine Triphosphate Production Research Articles

Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway.

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

Co-opted cytosolic proteins form condensate substructures within membranous replication organelles of a positive-strand RNA virus.

Positive-strand RNA viruses co-opt organellar membranes for biogenesis of viral replication organelles (VROs). Tombusviruses also co-opt pro-viral cytosolic proteins to VROs. It is currently not known what type of molecular organization keeps co-opted proteins sequestered within membranous VROs. In this study, we employed tomato bushy stunt virus (TBSV) and carnation Italian ringspot virus (CIRV) - Nicotiana benthamiana pathosystems to identify biomolecular condensate formation in VROs. We show that TBSV p33 and the CIRV p36 replication proteins sequester glycolytic and fermentation enzymes in unique condensate substructures associated with membranous VROs. We find that p33 and p36 form droplets in vitro driven by intrinsically disordered region. The replication protein organizes partitioning of co-opted host proteins into droplets. VRO-associated condensates are critical for local adenosine triphosphate production to support energy for virus replication. We find that co-opted endoplasmic reticulum membranes and actin filaments form meshworks within and around VRO condensates, contributing to unique composition and structure. We propose that p33/p36 organize liquid-liquid phase separation of co-opted concentrated host proteins in condensate substructures within membranous VROs. Overall, we demonstrate that subverted membranes and condensate substructures co-exist and are critical for VRO functions. The replication proteins induce and connect the two substructures within VROs.

Biological Insights into Energy Storage Technologies

In the face of increasing energy demands and environmental concerns, the search for sustainable and efficient energy storage technologies has intensified. This review presents a holistic survey of innovative solutions by examining biological approaches. The study proceeds through three thematic sections: Biological Fuel Cells and Battery Systems, Photosynthesis and Solar Energy Storage, and Energy Generation at the Cellular Level. The first section, Biological Fuel Cells and Battery Systems describes the integration of biological processes into energy storage mechanisms. The use of biological systems and their contribution to the development of environmentally friendly and high performance energy storage technologies are discussed. In the 2nd section, Photosynthesis and Solar Energy Storage are very prominent in sustainability and energy efficiency issues in terms of both energy production and energy source food production while reducing carbon dioxide with photosynthesis-based energy storage methods. Energy production at the cellular level is discussed in the last section, Adenosine triphosphate (ATP), which is necessary for the cell to perform processes such as growth, reproduction and response to environmental stimuli, is characterized as the primary fuel. ATP production is carried out by mitochondria in animal cells and chloroplast in plant cells. Energy storage at the cellular level is carried out by molecules such as glycogen and lipids in animal cells and starch in plant cells. Considering all three issues, it has been observed that biological-based energy storage methods have numerous advantages in terms of sustainability and energy efficiency. In application areas where engineering approaches are at the forefront, it is thought that it may be possible to design more sustainable and highly energy efficient energy production systems by gaining new perspectives with biology-based simulation studies.

Co-delivery of Paclitaxel/Atovaquone/Quercetin to regulate energy metabolism to reverse multidrug resistance in ovarian cancer by PLGA-PEG nanoparticles

Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR. Herein, we developed a PTX-ATO-QUE nanoparticle (PAQNPs) based on a PLGA-PEG nanoplatform capable of loading the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO), the glycolysis inhibitor quercetin (QUE), and the chemotherapeutic drug paclitaxel (PTX) to reverse MDR by inhibiting energy metabolism through multiple pathways. Mechanistically, PAQNPs could effectively inhibit the OXPHOS and glycolytic pathways of A2780/Taxol cells by suppressing the activities of mitochondrial complex III and hexokinase II (HK II), respectively, ultimately decreasing intracellular ATP levels in tumor cells. Energy depletion can effectively inhibit cell proliferation and reduce P-gp activity, increasing the chemotherapeutic drug PTX accumulation in the cells. Moreover, intracellular reactive oxygen species (ROS) is increased with PTX accumulation and leads to chemotherapy-resistant cell apoptosis. Furthermore, PAQNPs significantly inhibited tumor growth in the A2780/Taxol tumor-bearing NCG mice model. Immunohistochemical (IHC) analysis of tumor tissues revealed that P-gp expression was suppressed, demonstrating that PAQNPs are effective in reversing MDR in tumors by inducing energy depletion. In addition, the safety study results, including blood biochemical indices, major organ weights, and H&E staining images, showed that PAQNPs have a favorable in vivo safety profile. In summary, the results suggest that the combined inhibition of the two energy pathways, OXPHOS and glycolysis, can enhance chemotherapy efficacy and reverse MDR in ovarian cancer.

Integrated small RNA, transcriptome and physiological approaches provide insight into Taxodium hybrid 'Zhongshanshan' roots in acclimation to prolonged flooding.

Although Taxodium hybrid 'Zhongshanshan' 406 (Taxodium mucronatum Tenore×Taxodium distichum; Taxodium 406) is an extremely flooding-tolerant woody plant, the physiological and molecular mechanisms underlying acclimation of its roots to long-term flooding remain largely unknown. Thus, we exposed saplings of Taxodium 406 to either non-flooding (control) or flooding for 2months. Flooding resulted in reduced root biomass, which is in line with lower concentrations of citrate, α-ketoglutaric acid, fumaric acid, malic acid and adenosine triphosphate (ATP) in Taxodium 406 roots. Flooding led to elevated activities of pyruvate decarboxylase, alcohol dehydrogenase and lactate dehydrogenase, which is consistent with higher lactate concentration in the roots of Taxodium 406. Flooding brought about stimulated activities of superoxide dismutase and catalase and elevated reduced glutathione (GSH) concentration and GSH/oxidized glutathione, which is in agreement with reduced concentrations of O2- and H2O2 in Taxodium 406 roots. The levels of starch, soluble protein, indole-3-acetic acid, gibberellin A4 and jasmonate were decreased, whereas the concentrations of glucose, total non-structural carbohydrates, most amino acids and 1-aminocyclopropane-1-carboxylate (ACC) were improved in the roots of flooding-treated Taxodium 406. Underlying these changes in growth and physiological characteristics, 12,420 mRNAs and 42 miRNAs were significantly differentially expressed, and 886 miRNA-mRNA pairs were identified in the roots of flooding-exposed Taxodium 406. For instance, 1-aminocyclopropane-1-carboxylate synthase 8 (ACS8) was a target of Th-miR162-3p and 1-aminocyclopropane-1-carboxylate oxidase 4 (ACO4) was a target of Th-miR166i, and the downregulation of Th-miR162-3p and Th-miR166i results in the upregulation of ACS8 and ACO4, probably bringing about higher ACC content in flooding-treated roots. Overall, these results indicate that differentially expressed mRNA and miRNAs are involved in regulating tricarboxylic acid cycle, ATP production, fermentation, and metabolism of carbohydrates, amino acids and phytohormones, as well as reactive oxygen species detoxification of Taxodium 406 roots. These processes play pivotal roles in acclimation to flooding stress. These results will improve our understanding of the molecular and physiological bases underlying woody plant flooding acclimation and provide valuable insights into breeding-flooding tolerant trees.

Putative Molecular Mechanisms Underpinning the Inverse Roles of Mitochondrial Respiration and Heme Function in Lung Cancer and Alzheimer's Disease.

Mitochondria are the powerhouse of the cell. Mitochondria serve as the major source of oxidative stress. Impaired mitochondria produce less adenosine triphosphate (ATP) but generate more reactive oxygen species (ROS), which could be a major factor in the oxidative imbalance observed in Alzheimer's disease (AD). Well-balanced mitochondrial respiration is important for the proper functioning of cells and human health. Indeed, recent research has shown that elevated mitochondrial respiration underlies the development and therapy resistance of many types of cancer, whereas diminished mitochondrial respiration is linked to the pathogenesis of AD. Mitochondria govern several activities that are known to be changed in lung cancer, the largest cause of cancer-related mortality worldwide. Because of the significant dependence of lung cancer cells on mitochondrial respiration, numerous studies demonstrated that blocking mitochondrial activity is a potent strategy to treat lung cancer. Heme is a central factor in mitochondrial respiration/oxidative phosphorylation (OXPHOS), and its association with cancer is the subject of increased research in recent years. In neural cells, heme is a key component in mitochondrial respiration and the production of ATP. Here, we review the role of impaired heme metabolism in the etiology of AD. We discuss the numerous mitochondrial effects that may contribute to AD and cancer. In addition to emphasizing the significance of heme in the development of both AD and cancer, this review also identifies some possible biological connections between the development of the two diseases. This review explores shared biological mechanisms (Pin1, Wnt, and p53 signaling) in cancer and AD. In cancer, these mechanisms drive cell proliferation and tumorigenic functions, while in AD, they lead to cell death. Understanding these mechanisms may help advance treatments for both conditions. This review discusses precise information regarding common risk factors, such as aging, obesity, diabetes, and tobacco usage.

Light-activated NIR-II imaging-guided tumor therapy with enhanced HPTT/starvation cycle

Establishing a phototheranostic platform constructed by the second near-infrared (NIR-II) region has proved a revolutionary and promising strategy for cancer treatment. However, the antitumor effectiveness is severely limited by the monotonicity of the NIR-photothermal therapy (HPTT) modality and tumor thermotolerance caused by the production of heat shock proteins (HSPs). Here, a minimalistic approach is used to construct an organic nanoplatform (IFT@PEG-GOX NPs) with the reciprocal cyclic promotion of hypothermia and starvation treatments for NIR-II imaging-guided tumor therapy. After the enhanced permeability and retention (EPR) effect causes IFT@PEG-GOX NPs to accumulate in tumors, glucose oxidase (GOx)-mediated tumor starvation may obstruct the production of adenosine triphosphate (ATP) and downregulation heat shock proteins (HSPs), thereby reducing the thermotolerance of cells. After that, sensitized HPTT was activated and GOx's catalytic activity was increased by NIR laser irradiation. Then, there would be a subsequent, intensified inhibition of HSP along with an additional amplification of the GOx-mediated tumor starvation. As a consequence, the HPTT/Starvation therapy (ST) bidirectional cycle method is initiated, leading to a bidirectional cyclic enhancing impact of HPTT and ST and significantly better tumor suppression.

Childhood adverse life events and skeletal muscle mitochondrial function.

Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events "get under the skin" to influence physical well-being. Using data from the Study of Muscle, Mobility, and Aging (n = 879, 59% women), linear models examined whether adverse childhood events (i.e., physical abuse) were associated with two measures of skeletal muscle mitochondrial energetics in older adults: (i) maximal adenosine triphosphate production (ATPmax) and (ii) maximal state 3 respiration (Max OXPHOS). Forty-five percent of the sample reported experiencing one or more adverse childhood events. After adjustment, each additional event was associated with -0.08 SD (95% confidence interval = -0.13, -0.02) lower ATPmax. No association was observed with Max OXPHOS. Adverse childhood events are associated with lower ATP production in later life. Findings indicate that mitochondrial function may be a mechanism for understanding how early social stress influences health in later life.

Enzyme-Empowered "Two Birds with One Stone" Strategy for Amplifying Tumor Apoptosis and Metabolic Clearance.

Nanomedicine has reshaped the landscape of cancer treatment. However, its efficacy is still hampered by innate tumor defense systems that rely on adenosine triphosphate (ATP) for fuel, including damage repair, apoptosis resistance, and immune evasion. Inspired by the naturally enzymatic reaction of glucose oxidase (GOx) with glucose, here a novel "two birds with one stone" technique for amplifying enzyme-mediated tumor apoptosis and enzyme-promoted metabolic clearance is proposed and achieved using GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G). Re@ReP-G reduces ATP production while increasing H2O2 concentrations in the tumor microenvironment through GOx-induced enzymatic oxidation, which in turn results in the downregulation of defense (HSP70 and HSP90) and anti-apoptotic Bcl-2 proteins, the upregulation of pro-apoptotic Bax, and the release of cytochrome c. These processes are further facilitated by laser-induced hyperthermia effect, ultimately leading to severe tumor apoptosis. As an enzymatic byproduct, H2O2 catalyzes the conversion of rhenium nanoclusters in Re@ReP-G nanostructures into rhenate from the outside in, which accelerates their metabolic clearance in vivo. This Re@ReP-G-based "two birds with one stone" therapeutic strategy provides an effective tool for amplifying tumor apoptosis and safe metabolic mechanisms.

Anaerobic propionic acid production via succinate pathway at extremely low pH

Propionic acid, a C-3 platform chemical with applications in a wide variety of industries, is currently produced via petroleum-based pathway. Bio-propionic acid can be a promising alternative to petroleum-based one. However, the bio-production of propionic acid is easily inhibited by low pH (<4.5). Typical vegetable wastes, cabbage and Chinese cabbage were fermented for propionic acid production in leaching bed reactors (LBRs) without pH control. The highest propionic acid production reached up to 12.50 g COD/L in LBR with large-size cabbage, corresponding to cumulative yields of 0.27 g COD/g·VSremoval. Without pH control, pH in this reactor was ∼3.5 during the whole operation period. Extremely low pH regulated the intracellular NADH/NAD+ balance and induced a relatively reductive micro-environment. Adenosine triphosphate (ATP) consumption reactions were triggered to maintain the intracellular proton balance and metabolic activity; thus, the relative abundance of H+-ATPase-related genes was increased to maximize ATP production. The low-pH inducible micro-environment selected Lactobacillus fermentum and Lactobacillus plantarum as dominant species in the microbial community. Succinate pathway was identified as the main fermentative pathway for propionic acid production with both cabbage and Chinese cabbage wastes, which maximized energy generation in propionic acid fermentation. This work unveils a unique propionic acid production pathway from vegetable waste biomass and offers a promising route for waste conversion towards a circular bioeconomy.

Delivering cells via ECM mimetic hydrogel microspheres for promoting the reconstruction of rat lumbar nucleus pulposus

Nucleus pulposus (NP) discectomy is a clinical procedure for the treatment of late-stage intervertebral disc (IVD) degeneration; however, it is associated with the potential for serious complications. The reconstruction of the NP tissue presents challenges due to its avascular structure and prolonged compression within the IVD. In this study, we have developed a novel biomimetic hydrogel microsphere composed of gelatin methacryloyl (GelMA) and fucoidan, a polysaccharide derived from marine brown seaweed, to mimic the extracellular matrix (ECM) of the native NP. The GelMA and fucoidan (GelMA@FD) hydrogel microspheres demonstrate favorable cytocompatibility and significantly enhance the synthesis of matrix components in nucleus pulposus cells (NPCs), including aggrecan and type II collagen. Transcriptome sequencing analysis demonstrates a correlation between the augmentation of matrix synthesis and the enrichment of genes and pathways related to mitochondrial function. Subsequent molecular investigations provide evidence that NPCs cultured on GelMA@FD exhibit enhanced mitochondrial functions, including elevated adenosine triphosphate production and respiratory chain factor expression, alongside a reduction in mitochondrial reactive oxygen species. When implantated into rat lumbar IVDs that have undergone discectomy, the incorporation of NPCs within GelMA@FD hydrogel microspheres facilitates the regeneration of the NP and reinstates its structural and biomechanical properties. This is substantiated by the observed augmentation in IVD disc height and water content within the NP compartment. Collectively, these results demonstrate the potential of employing cell-laden GelMA@FD hydrogel microspheres as a promising strategy for NP regeneration in degenerated IVDs.

MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice

BackgroundMitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes.MethodsWe generated Morn2–/– mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc.ResultsThe Morn2–/– mice were infertile, and their sperm showed severe motility defects. Morn2–/– sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity.ConclusionsOur study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencinganalysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential,and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.

Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Hypoxia-inducible factor-2α promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence and affects approximately one-third of adults, owing to high-fat dietary habits and a sedentary lifestyle. The role of hypoxia-inducible factor 2α (HIF-2α) in NAFLD progression remains unknown. This study aimed to investigate the effects of chronic hypoxia on NAFLD progression by examining the role of hypoxia-inducible factor 2α (HIF-2α) activation and that of hepatic stellate cell (HSC)-derived myofibroblasts through glutaminolysis. We hypothesised that hypoxia exacerbates NAFLD by promoting HIF-2α upregulation and inhibiting phosphorylated yes-associated protein (YAP), and that increasing YAP expression enhances HSC-derived myofibroblasts. We studied patients with NAFLD living at high altitudes, as well as animal models and cultured cells. The results revealed significant increases in HSC-derived myofibroblasts and collagen accumulation caused by HIF-2α and YAP upregulation, both in patients and in a mouse model for hypoxia and NAFLD. HIF-2α and HIF-2α-dependent YAP downregulation reduced HSC activation and myofibroblast levels in persistent chronic hypoxia. Furthermore, hypoxia-induced HIF-2α upregulation promoted YAP and inhibited YAP phosphorylation, leading to glutaminase 1 (GLS1), SLC38A1, α-SMA, and Collagen-1 overexpression. Additionally, hypoxia restored mitochondrial adenosine triphosphate production and reactive oxygen species (ROS) overproduction. Thus, chronic hypoxia-induced HIF-2α activation enhances fibrosis and NAFLD progression by restoring mitochondrial ROS production and glutaminase-1-induced glutaminolysis, which is mediated through the inhibition of YAP phosphorylation and increased YAP nuclear translocation. In summary, HIF-2α plays a pivotal role in NAFLD progression during chronic hypoxia.

LINC00665 promotes glycolysis in lung adenocarcinoma cells via the let-7c-5p/HMMR axis.

Lung adenocarcinoma (LUAD) is one of the most lethal and common malignancies. The energy metabolism of LUAD is a critical factor affecting its malignant progression, and research on this topic can aid in the development of novel cancer treatment targets.Bioinformatics analysis of the expression of long non-coding RNA (lncRNA) LINC00665 in LUAD was performed. Downstream regulatory molecules of LINC00665 were predicted using the StarBase database. We used quantitative reverse transcription polymerase chain reaction and western blot to measure the expression at mRNA and protein levels, respectively. The effects of the LINC00665/let-7c-5p/HMMR axis on cell viability in vitro were tested by CCK-8 assay. The regulatory effects on glycolysis were analyzed by extracellular acidification rate, oxygen consumption rate, glucose uptake, adenosine triphosphate production, and lactate production. The predicted competitive endogenous RNA mechanism between LINC00665 and let-7c-5p/HMMR was verified by a dual-luciferase reporter gene assay.LINC00665 was upregulated in LUAD. Silencing LINC00665 inhibited tumor proliferation and reduced the glycolytic activity of tumor cells. Additionally, the expression of LINC00665 had a negative correlation with that of let-7c-5p, while the expression of HMMR was remarkably inhibited by let-7c-5p. HMMR could affect the development of LUAD by influencing glycolytic capacity. Mechanistically, LINC00665 acted as a molecular sponge to absorb let-7c-5p and targeted HMMR. Transfection of let-7c-5p inhibitor or overexpression of HMMR plasmid could reverse the inhibition in proliferation and glycolysis of LUAD cells induced by silencing of LINC00665.In summary, this study demonstrated that the LINC00665/let-7c-5p/HMMR regulatory axis promoted the tumorigenesis of LUAD by enhancing aerobic glycolysis, suggesting that this regulatory axis was an effective target for inhibiting LUAD progression and providing theoretical support for the development of new drugs for LUAD.

Light stimulation of mitochondria reduces blood glucose levels.

Mitochondria regulate metabolism, but solar light influences its rate. Photobiomodulation (PBM) with red light (670 nm) increases mitochondrial membrane potentials and adenosine triphosphate production and may increase glucose demand. Here we show, with a glucose tolerance test, that PBM of normal subjects significantly reduces blood sugar levels. A 15 min exposure to 670 nm light reduced the degree of blood glucose elevation following glucose intake by 27.7%, integrated over 2 h after the glucose challenge. Maximum glucose spiking was reduced by 7.5%. Consequently, PBM with 670 nm light can be used to reduce blood glucose spikes following meals. This intervention may reduce damaging fluctuations of blood glucose on the body.

The role of CoQ10 in embryonic development.

Coenzyme Q10 (CoQ10) is a natural component widely present in the inner membrane of mitochondria. CoQ10 functions as a key cofactor for adenosine triphosphate (ATP) production and exhibits antioxidant properties in vivo. Mitochondria, as the energy supply center of cells, play a crucial role in germ cell maturation and embryonic development, a complicated process of cell division and cellular differentiation that transforms from a single cell (zygote) to a multicellular organism (fetus). Here, we discuss the effects of CoQ10 on oocyte maturation and the important role of CoQ10 in the growth of various organs during different stages of fetal development. These allowed us to gain a deeper understanding of the pathophysiology of embryonic development and the potential role of CoQ10 in improving fertility quality. They also provide a reference for further developing its application in clinical treatments.

Comprehensive overview of the role of mitochondrial dysfunction in the pathogenesis of acute kidney ischemia-reperfusion injury: a narrative review.

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.