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Structure of mitochondria. The mitochondrion is composed of a double membrane: the inner membrane and the outer membrane. Between these membranes is the intra-membrane space. The inner membrane forms invaginations called ridges where the OXPHOS complexes are located. The mitochondrial matrix contains several copies of mitochondrial circular DNA and ribosomes. Mitochondria image adapted from Smart. Available online: https://smart.servier.com (accessed on 10 August 2021).
Source publication
Mitochondria are the energy center of the cell. They are found in the cell cytoplasm as dynamic networks where they adapt energy production based on the cell’s needs. They are also at the center of the proinflammatory response and have essential roles in the response against pathogenic infections. Mitochondria are a major site for production of Rea...
Context in source publication
Citations
... Notably, the excessive generation of mitochondrial superoxide anions induced by elevated sugar and fat levels serves as a primary trigger for cellular injury (Andreas et al., 2019;Han et al., 2021;Pruett et al., 2022). The pivotal role of oxidative stress-induced mitochondrial dysfunction in SDM pathogenesis has garnered widespread attention (Yin and Ding, 2013;Andrieux et al., 2021;Sulkshane et al., 2021). Given mitochondria's central role in cellular oxidative stress, we identified mitochondria-related genes via the MitoCarta3.0 database. ...
Background
The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM’s renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics.
Aims
The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment.
Methods
Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet β cells.
Results
In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, β-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3β protein in islet cells ( p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers ( p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet β cells.
Conclusion
Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3β pathway plays an important regulatory role in this process.
... This process is mediated by a series of enzyme supercomplexes, called the electron transport chain (ETC), which are located in the inner mitochondrial membrane. 62 The energy released by the electron transfer is used to pump protons (H+) across the inner mitochondrial membrane, creating an electrochemical gradient (mitochondrial membrane potential, ΔΨm) which drives ATP synthase for ATP synthesis. TNF-α and IFN-γ also can disrupt cardiomyocyte metabolism, decreasing basal and maximal respiration and ATP production. ...
This review article highlights the significant impact of mitochondrial dysfunction on Chagas disease (CD) cardiomyopathy. By examining the existing body of research, it provides a comprehensive anal- ysis of the detrimental consequences resulting from impaired mitochondrial function in this cardiac con- dition. We review new intricate relationship between CD cardiomyopathy, inflammatory response, mito- chondrial dysfunction and energy disbalance, elucidating some molecular mechanisms and pathways involved. This review not only enhances our understanding of the disease pathogenesis but also emphasizes the crucial role of mitochondria in cardiac function and its potential as a therapeutic target for mitigating CD cardiomyopathy.
... Mitochondrion, which provides energy for cell activity, is the metabolic center of cells [13]. According to the endosymbiont hypothesis, "mitochondria" is coined to describe a primordial cellular component resulting from the fusion of an endosymbiotic alphaproteobacterium with a host cell that shares ancestry with Asgard Archaea., eventually developing into eukaryotic organelles [14]. ...
Background
Plant mitochondria exist and function in a special way, this third-kind genetic material is essential for plant growth and development. However, its complex and highly variable genome structure lead to a poor understanding compared with chloroplasts.
Results
With the help of HIFI sequencing, we obtained new insights of their structure and functions. Machilus pauhoi (Magnoliaceae), an indigenous species, showcases a profusion of metabolites, elegant growth traits like bright red fresh leaves and straight trunk. Thus, we initially curated complete reference mitochondrial genomes for Machilus pauhoi. Though still regarded as complex structure, a 775 Kb two-circle physical map exhibiting simplification trend through one long lateral repeat region in ANA grade. Comparisons of consistent sequences revealed significant large-scale and inclined rearrangements within both cytoplasmic and nuclear genomes. Furthermore, the identification of lateral transfers from chloroplast to mitochondrial genome highlighted the consistent capture of functional genes such as petN. Besides, transferred sequences displayed chromosomal preference in nuclear genome, including genes like cytb, ATP9 and mRpL2. Aberrant selective pressure occurred for ccmB in Magnoliales though mitogenomes bore a greater burden of pressure compared to genes in the chloroplast. We also presented the expression of mtgenes , emphasizing a relatively functional concentration in no chloroplast tissues.
Conclusion
Eventually, the assembly of our newly acquired mitogenome contributes valuable insights into the evolutionary patterns observed in higher plant mitogenomes, thereby establishing a robust foundation for future industrial advancements in functional exploration of forest species.
... Research on mitochondrial disorders and immunity has garnered signi cant interest. Mitochondria play crucial roles in the proin ammatory response, in uencing the activation and differentiation of immune cells [20,21]. Moreover, several signals derived from mitochondria are involved in the activation of NLRP3, NLRP6, and other in ammasomes [22]. ...
Background
Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of ovarian function before the age of 40. While mitochondrial dysfunction and immune disorders are believed to contribute to ovarian damage in POI, the interplay between these factors remains understudied in patients with this condition.
Methods
In this research, transcriptomic data related to POI were obtained from the NCBI GEO database. Hub biomarkers were identified through the construction of a protein‒protein interaction (PPI) network and further validated using RT‒qPCR. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. Comprehensive investigation into the mitochondrial and immune profiles of POI patients was carried out through correlation analysis. Furthermore, potential therapeutic agents were predicted utilizing the cMap database.
Results
A total of 119 mitochondria-related differentially expressed genes (MitoDEGs) were pinpointed, showing significant enrichment in metabolic pathways. Among these genes, Hadhb, Cpt1a, Mrpl12, and Mrps7 were confirmed both in a POI model and in human granulosa cells (GCs), where they were found to accumulate in GCs and theca cells. Immune analysis revealed variations in macrophages, monocytes, and 15 other immune cell types between the POI and control groups. Notably, strong correlations were observed between seven hub-MitoDEGs (Hadhb, Cpt1a, Cpt2, Mrpl12, Mrps7, Mrps51, and Eci1) and various aspects such as mitochondrial respiratory complexes, dynamics, mitophagy, mitochondrial metabolism, immune-related genes, and immunocytes. Additionally, nine potential drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, and pizotifen) targeting key genes were identified.
Conclusions
Our results highlight the crosstalk between mitochondrial function and the immune response in the development of POI. The identification of MitoDEGs could lead to reliable biomarkers for the early diagnosis, monitoring and personalized treatment of POI patients.
... Cuando el insulto patológico persiste, se incrementa la demanda de oxígeno por la elevada actividad celular y en consecuencia la entrega del oxígeno al torrente sanguíneo disminuye y ocasiona más hipoxemia, lo que produce déficit de la fosforilación oxidativa, incremento del nitrógeno y los niveles de ROS intracelular. Esto desencadena disfunciones mitocondriales con pérdida del potencial de membrana, el cual aumenta la permeabilidad celular e incrementa aún más la respuesta inflamatoria por la liberación del ADNmt.11 En las mitocondrias se altera la composición proteica de la cadena de transporte de electrones, producto de la respuesta inflamatoria, es decir que las moléculas de NADH y FADH2 formadas en el ciclo de Krebs decaen en el transporte de electrones. ...
Mitochondria play an important role in cell energy metabolism due to the main function of producing biologically available energy in the form of adenosine triphosphate (ATP), through biochemical processes such as oxidative phospho-rylation, beta oxidation of fatty acids and the Krebs cycle. Acute respiratory distress syndrome is a severe lung disease characterized by the appearance of diffuse alveolar infiltrates, dysregulated immune response and alveolocapillary injury that limits gas exchange. Alveolar cells maintain an oxygen tension of 5% and mitochondria consume oxygen through the cytochrome c oxidase enzyme in the electron transport chain, allowing ATP production. The reduction in oxygen consumption is crucial in mitochondrial damage, as mitochondria are sensitive to hypoxemia, affecting the transfer of molecules in the electron transport chain that disrupt the Krebs cycle. Hypoxia due to hypoxemia affects mitochondrial fusion and fission, while OXPHOS remodels, mainly in complex I, to maintain mitochondrial integrity. Lack of oxygen activates hypoxia-inducible factors, generating oxidative stress, acidosis and cell damage; therefore, this review aims to describe mitochondrial adaptations in acute respiratory distress syndrome.
... [22] Furthermore, these intrinsic lethal stimuli, along with DNA damage and metabolic and ER stresses, among others, are thought to induce apoptotic molecules such as Bid, Bax, and Bak proteins. In consequence, these multiple death-inducing stimuli, Bid, Bax, and Bak, could induce the release of cytochrome C. [23] In addition, pro-inflammatory mediators known to trigger the extrinsic pathway of apoptosis could be linked with cytochrome c release in the mitochondria through the caspases 8 and 10/Bid/ tBid/Bax/Bak route following the induction of death receptors (DR) (e.g., TRAILR and Fas). In this way, pro-inflammatory mediators such as interleukin (IL)-6, IL-1, and tumor necrosis factor may decrease albumin synthesis. ...
Objective: This study investigates the role of Apoptotic Protease Activating Factor-1 (APAF-1) in CD4+ cell depletion among human immunodeficiency virus (HIV) patients.
Materials and Methods: This is a cross-sectional study in which 105 participants were enrolled, including 60 confirmed HIV-positive patients and 45 HIV-negative controls. HIV-positive patients were further divided based on CD4+ cell counts: Group 1 (<200), Group 2 (200–499), and Group 3 (≥500). An enzyme-linked immunoassay was used to measure APAF-1 levels, and CD4+ T-cell counts were enumerated using a Cyflow counter. Independent student’s t-test, Kruskal-Wallis, and Spearman’s correlation were utilized as needed.
Results: Results showed significant reductions in lymphocytes, platelets, red blood cells, hemoglobin, albumin, and CD4+ cell values among HIV-infected individuals compared to controls. Conversely, APAF-1 and total protein levels were elevated in HIV-positive patients. Among HIV-positive groups, those with CD4+ cell counts <200 exhibited the highest median serum APAF-1 concentration. However, these differences were not statistically significant when compared with the other seropositive groups with CD4+ cell counts between 200 and 499 (P = 0.6726) and CD4+ cell counts of 500 or greater (P = 0.4325). The control group had the lowest median SAPAF-1 concentration, significantly different from HIV-positive groups. Positive correlations were observed between CD4+ counts and lymphocytes, hemoglobin, and hypoalbuminemia, while negative correlations were found between these parameters and APAF-1 levels.
Conclusion: APAF-1 is a host factor that potentially contributes to CD4+ cell depletion. Similarly, APAF-1, serum total protein, and albumin levels were found to be predictive of disease progression and could serve as valuable diagnostic biomarkers in the monitoring of HIV/AIDS.
... This study investigated mitochondrial function due to its regulatory role in infection, inflammation, recovery, and cellular homeostasis [6]. Viral infections cause excessive production of mitochondrial reactive oxygen species, which disrupt the mitochondrial morphology and function [7]. Mitochondrial insufficiency is related to aging [8], immune dysfunction [9,10], and metabolic dysregulation [11]. ...
Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVID biomarkers in non-hospitalized patients. Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers. The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.
... The brain in particular is undergoing rapid post-natal expansion and requires efficiently functioning mitochondria with a steady supply of oxygen to meet energy demands. Mitochondria coupled with oxygen are also responsible for immune response, calcium buffering, and regulating reactive oxygen species (ROS) production, which can trigger programmed cell death (5)(6)(7)(8). A delicate balance exists between adequate oxygen for growth and development yet avoiding excess oxygen that can lead to toxicity and cell death. ...
Despite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be life-saving for term and preterm neonates in the resuscitation period and beyond, however use of oxygen in the neonatal period must be judicious as there can be toxic effects. Newborns experience substantial hemodynamic changes at birth, rapid energy consumption, and decreased antioxidant capacity, which requires a delicate balance of sufficient oxygen while mitigating reactive oxygen species causing oxidative stress. In this review, we will discuss the physiology of neonates in relation to hypoxia and hyperoxic injury, the history of supplemental oxygen in the delivery room and beyond, supporting clinical research guiding trends for oxygen therapy in neonatal care, current practices, and future directions.
... Consequently, mitochondria may play a central role in tumor development, including BC. Several studies suggest a potential link between mitochondrial dysfunction and BC 34,35 . Tumor tissues from BC patients might exhibit abnormalities in mitochondrial function, including mitochondrial DNA mutations, alterations in mitochondrial membrane potential, and increased www.nature.com/scientificreports/ ...
Bladder cancer (BC) is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Mitochondrial Dysfunction is involved in the progression of BC. This study aimed to developed a novel diagnostic model based on mitochondria-related genes (MRGs) for BC patients using Machine Learning. In this study, we analyzed GSE13507 datasets and identified 752 DE-MRGs in BC specimens. Functional enrichment analysis uncovered the significant roles of 752 DE-MRGs in key processes such as cellular and organ development, as well as gene regulation. The analysis revealed the crucial functions of these genes in transcriptional regulation and protein-DNA interactions. Then, we performed LASSO and SVM-RFE, and identified four critical diagnostic genes including GLRX2, NMT1, OXSM and TRAF3IP3. Based on the above four genes, we developed a novel diagnostic model whose diagnostic value was confirmed in GSE13507, GSE3167 and GSE37816 datasets. Moreover, we reported the expressing pattern of GLRX2, NMT1, OXSM and TRAF3IP3 in BC samples. Immune cell infiltration analysis revealed that the four genes were associated with several immune cells. Finally, we performed RT-PCR and confirmed NMT1 was highly expressed in BC cells. Functional experiments revealed that knockdown of NMT1 suppressed the proliferation of BC cells. Overall, we have formulated a diagnostic potential that offered a comprehensive framework for delving into the underlying mechanisms of BC. Before proceeding with clinical implementation, it is essential to undertake further investigative efforts to validate its diagnostic effectiveness in BC patients.
... Mitochondria with stable structure and function play a pivotal role in antioxidant effect [109]. Overproduction of ROS can damage mitochondrial integrity, and activated vitamin D interacts with vitamin D receptors to counter such damage and stabilize metabolism in brain nerve cells [110]. ...
Objective
To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD).
Methods
Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1.
Results
48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners’ parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners’ teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42).
Conclusion
The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings.
