ABSTRACT
Synthetic electroactive microbial consortia, which include exoelectrogenic and electrotrophic communities, catalyze the exchange of chemical and electrical energy in cascade metabolic reactions among different microbial strains. In comparison to a single strain, a community-based organisation that assigns tasks to multiple strains enables a broader feedstock spectrum, faster bi-directional electron transfer, and greater robustness. Therefore, the electroactive microbial consortia held great promise for a variety of applications such as bioelectricity and biohydrogen production, wastewater treatment, bioremediation, carbon and nitrogen fixation, and synthesis of biofuels, inorganic nanomaterials, and polymers. This review firstly summarized the mechanisms of biotic-abiotic interfacial electron transfer as well as biotic-biotic interspecific electron transfer in synthetic electroactive microbial consortia. This was followed by introducing the network of substance and energy metabolism in a synthetic electroactive microbial consortia designed by using the "division-of-labor" principle. Then, the strategies for engineering synthetic electroactive microbial consortiums were explored, which included intercellular communications optimization and ecological niche optimization. We further discussed the specific applications of synthetic electroactive microbial consortia. For instance, the synthetic exoelectrogenic communities were applied to biomass generation power technology, biophotovoltaics for the generation of renewable energy and the fixation of CO2. Moreover, the synthetic electrotrophic communities were applied to light-driven N2 fixation. Finally, this review prospected future research of the synthetic electroactive microbial consortia.
Subject(s)
Microbial Consortia , Synthetic Biology , Electron Transport , Electricity , Biodegradation, EnvironmentalABSTRACT
Facing the increasingly severe energy shortage and environmental pollution, electrocatalytic processes using electroactive microorganisms provide a new alternative for achieving environmental-friendly production. Because of its unique respiratory mode and electron transfer ability, Shewanella oneidensis MR-1 has been widely used in the fields of microbial fuel cell, bioelectrosynthesis of value-added chemicals, metal waste treatment and environmental remediation system. The electrochemically active biofilm of S. oneidensis MR-1 is an excellent carrier for transferring the electrons of the electroactive microorganisms. The formation of electrochemically active biofilm is a dynamic and complex process, which is affected by many factors, such as electrode materials, culture conditions, strains and their metabolism. The electrochemically active biofilm plays a very important role in enhancing bacterial environmental stress resistance, improving nutrient uptake and electron transfer efficiency. This paper reviewed the formation process, influencing factors and applications of S. oneidensis MR-1 biofilm in bio-energy, bioremediation and biosensing, with the aim to facilitate and expand its further application.
Subject(s)
Bioelectric Energy Sources/microbiology , Biofilms , Electrodes , Electron Transport , Shewanella/metabolismABSTRACT
Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.
Subject(s)
Humans , Oxidative Phosphorylation , Berberine , Electron Transport , Mitochondria , Leukemia, Myeloid, Acute , Isocitrate DehydrogenaseABSTRACT
17α hydroxylase is a key enzyme for the conversion of progesterone to prepare various progestational drug intermediates. To improve the specific hydroxylation capability of this enzyme in steroid biocatalysis, the CYP260A1 derived from cellulose-mucilaginous bacteria Sorangium cellulosum Soce56 and the Fpr and bovine adrenal-derived Adx4-108 derived from Escherichia coli str. K-12 were used to construct a new electron transfer system for the conversion of progesterone. Selective mutation of CYP260A1 resulted in a mutant S276I with significantly enhanced 17α hydroxylase activity, and the yield of 17α-OH progesterone reached 58% after optimization of the catalytic system in vitro. In addition, the effect of phosphorylation of the ferredoxin Adx4-108 on 17α hydroxyl activity was evaluated using a targeted mutation technique, and the results showed that the mutation Adx4-108T69E transferred electrons to S276I more efficiently, which further enhanced the catalytic specificity in the C17 position of progesterone, and the yield of 17α-OH progesterone was eventually increased to 74%. This study provides a new option for the production of 17α-OH progesterone by specific transformation of bacterial-derived 17α hydroxylase, and lays a theoretical foundation for the industrial production of progesterone analogs using biotransformation method.
Subject(s)
Animals , Cattle , Progesterone/metabolism , Hydroxylation , Biocatalysis , Electron Transport , Mixed Function Oxygenases/metabolismABSTRACT
OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing.@*METHODS@#Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis.@*CONCLUSION@#Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.
Subject(s)
Child , Humans , China , DNA Copy Number Variations , Electron Transport , Mutation , NADH Dehydrogenase/genetics , PedigreeABSTRACT
Exoelectrogenic microorganisms are the research basis of microbial electrochemical technologies such as microbial fuel cells, electrolytic cells and electrosynthesis. However, their applications are restricted in organic degradation, power generation, seawater desalination, bioremediation, and biosensors due to the weak ability of biofilm formation and the low extracellular electron transfer (EET) efficiency between exoelectrogenic microorganisms and electrode. Therefore, engineering optimization of interaction between exoelectrogenic microorganisms and electrode interface recently has been the research focus. In this article, we review the updated progress in strategies for enhancing microbe-electrode interactions based on microbial engineering modifications, with a focus on the applicability and limitations of these strategies. In addition, we also address research prospects of enhancing the interaction between electroactive cells and electrodes.
Subject(s)
Bioelectric Energy Sources , Biofilms , Electrodes , Electron Transport , ElectronsABSTRACT
BACKGROUND: Urushiols are pro-electrophilic haptens that cause severe contact dermatitis mediated by CD8+ effector T-cells and downregulated by CD4+ T-cells. However, the molecular mechanism by which urushiols stimulate innate immunity in the initial stages of this allergic reaction is poorly understood. Here we explore the sub-cellular mechanisms by which urushiols initiate the allergic response. RESULTS: Electron microscopy observations of mouse ears exposed to litreol (3-n-pentadecyl-10-enyl-catechol]) showed keratinocytes containing swollen mitochondria with round electron-dense inclusion bodies in the matrix. Biochemical analyses of sub-mitochondrial fractions revealed an inhibitory effect of urushiols on electron flow through the mitochondrial respiratory chain, which requires both the aliphatic and catecholic moieties of these allergens. Moreover, urushiols extracted from poison ivy/oak (mixtures of 3-n-pentadecyl-8,11,13 enyl/3-n-heptadecyl-8,11 enyl catechol) exerted a higher inhibitory effect on mitochondrial respiration than did pentadecyl catechol or litreol, indicating that the higher number of unsaturations in the aliphatic chain, stronger the allergenicity of urushiols. Furthermore, the analysis of radioactive proteins isolated from mitochondria incubated with 3H-litreol, indicated that this urushiol was bound to cytochrome c1. According to the proximity of cytochromes c1 and b, functional evidence indicated the site of electron flow inhibition was within complex III, in between cytochromes bL (cyt b566) and bH (cyt b562). CONCLUSION: Our data provide functional and molecular evidence indicating that the interruption of the mitochondrial electron transport chain constitutes an important mechanism by which urushiols initiates the allergic response. Thus, mitochondria may constitute a source of cellular targets for generating neoantigens involved in the T-cell mediated allergy induced by urushiols.
Subject(s)
Animals , Mice , Allergens , Cytochromes b , Catechols , Cytochromes c1 , Cytochromes c , Electron Transport , MitochondriaABSTRACT
The mitochondrial respiratory chain supercomplex (mitoSC) is a complex super-assembly formed by free complexes on the mitochondrial inner membrane respiratory chain through the interaction between their subunits, mainly including mitoSCI+III+IV, mitoSCI+III, mitoSCIII+IV, high molecular weight mitoSC (HMW mitoSC) and mitochondrial metacomplex (mitoMC). mitoSC has been shown to improve the efficiency of electron transport in the respiratory chain and reduce the production of reactive oxygen species. The species and content of mitoSC change in different tissues in aging and many mitochondria-related diseases. By summarizing the structure and function of mitoSC in different tissues of human and mammals, and the changes of mitoSC under conditions of aging, heart disease, type 2 diabetes, cancer and genetic defects, this review focuses on the effects of exercise on mitoSC and its related regulation mechanisms in order to offer an insight for exercise interventions in mitochondria-related diseases.
Subject(s)
Animals , Humans , Electron Transport , Exercise , Mitochondria , Mitochondrial Diseases , Mitochondrial MembranesABSTRACT
Exoelectrogens are promising for a wide variety of potential applications in the areas of environment and energy, which convert chemical energy from organic matter into electrical energy by extracellular electrons transfer (EET). Microorganisms with different mechanisms and EET efficiencies have been elucidated. However, the practical applications of exoelectrogens are limited by their fundamental features. At present, it is difficult to realize the extensive application of exoelectrogens in complex and diverse environments by means of traditional engineering strategies such as rational design and directed evolution. The exoelectrogens with excellent performance in environments can be screened with efficient strain identification technologies, which promote the widespread applications of exoelectrogens. The aims of this review are to summarize the methods of screening based on different types of exoelectrogens, and to outline future research directions of strain screening.
Subject(s)
Bioelectric Energy Sources , Electricity , Electron TransportABSTRACT
BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.RESULTS: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.CONCLUSION: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.
Subject(s)
Animals , Mice , Adenosine Triphosphate , AMP-Activated Protein Kinases , Blotting, Western , Cell Survival , Electron Transport , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Fatty Acids, Nonesterified , Insulin , Insulin-Secreting Cells , Metformin , NADPH Oxidases , Oxidative Stress , Phosphorylation , Polymerase Chain Reaction , Reactive Oxygen Species , rho-Associated Kinases , RNA, MessengerABSTRACT
Poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] belongs to the polyhydroxyalkanoates (PHA) family and possesses promising properties including biocompatibility and biodegradability. In this study, we directly synthesized P(3HB-co-LA) with glucose by introducing the β-ketothiolase and acetoacetyl-CoA reductase from Ralstonia eutropha, the engineered propionate CoA transferase from Clostridium propionicum and the engineered polyhydroxyalkanoate synthase from Pseudomonas fluorescens strain 2P24 into Escherichia coli. The polymer content was 83.9% (W/W), and the molar percentage of lactate reached 1.6%. On this basis, in order to accumulate lactate, we reduced the activity of respiratory chain by deleting the ubiX gene, which is involved in the synthesis of coenzyme Q8. Moreover, we removed the dld gene to avoid the conversion of lactate to pyruvate during the fermentation. With these manipulations, the molar percentage of lactate in the polymer was improved to 14.1%, with an 81.7% (W/W) of polymer content. The test results indicated that the strategy of reducing the activity of respiratory chain effectively increased the lactate units in the polymer, and it contributed a new approach to change the content of monomer components in the polymer.
Subject(s)
3-Hydroxybutyric Acid , Electron Transport , Escherichia coli , Lactic Acid , Metabolic Engineering , PolyestersABSTRACT
PURPOSE: Leigh syndrome (LS) is a rare, progressive neurodegenerative disorder with characteristic abnormalities in the central nervous system. Such patients present with heterogeneous clinical symptoms and genetic abnormalities; thus, prognosis is difficult to anticipate. The present study investigates whether distinct patient characteristics are associated with mitochondrial DNA (mtDNA) mutation in LS patients. METHODS: We retrospectively analyzed data from patients diagnosed with LS at our hospital who were assessed using genomic sequencing of mtDNA. A subgroup analysis was performed to divide patients according to the mtDNA sequencing results. RESULTS: Among the 85 patients enrolled, 18 had mtDNA mutations. Most patients had lactic acidosis and a lactate/pyruvate ratio above 20, indicating respiratory chain abnormalities. In the subgroup analysis, the mutation group had a significantly higher female-to-male ratio, alanine level, ocular involvement, and midbrain and medulla abnormalities on magnetic resonance imaging (MRI). CONCLUSION: The subgroup analysis indicates that mtDNA sequencing is recommended for female patients, or those who exhibit ocular involvement, high alanine levels, or MRI findings with lesions in the midbrain and medulla.
Subject(s)
Female , Humans , Acidosis, Lactic , Alanine , Brain Stem , Central Nervous System , DNA, Mitochondrial , Electron Transport , Leigh Disease , Magnetic Resonance Imaging , Mesencephalon , Mitochondria , Neurodegenerative Diseases , Prognosis , Retrospective StudiesABSTRACT
In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.
Subject(s)
Adenosine Triphosphate , Aldehyde Dehydrogenase , Cytosol , Electron Transport , Energy Metabolism , Fermentation , Glucose , Lactic Acid , Metabolism , Mitochondria , NAD , Oxidative Phosphorylation , Oxygen , SymbiosisABSTRACT
BACKGROUND: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients. METHODS: Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing. RESULTS: Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.
Subject(s)
Humans , Brain Neoplasms , Brain , Carcinogenesis , Codon , DNA, Mitochondrial , Electron Transport , Malaysia , Mitochondria , Neurodegenerative Diseases , Reactive Oxygen Species , Sequence Analysis, DNAABSTRACT
Myoblast fusion depends on mitochondrial integrity and intracellular Ca²⁺ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with [Ca²⁺]i regulation in normal and mitochondrial DNA-depleted (ρ0) L6 myoblasts. The ρ0 myoblasts showed impaired myotube formation. The inwardly rectifying K⁺ current (I(Kir)) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated Ca²⁺ channel and Ca²⁺-activated K⁺ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the I(Kir). The ρ0 myoblasts showed depolarized resting membrane potential and higher basal [Ca²⁺]ᵢ. Our results demonstrated the specific downregulation of I(Kir) by dysfunctional mitochondria. The resultant depolarization and altered Ca²⁺ signaling might be associated with impaired myoblast fusion in ρ0 myoblasts.
Subject(s)
Antimycin A , Down-Regulation , Electron Transport , Ion Channels , Membrane Potentials , Mitochondria , Muscle Development , Muscle Fibers, Skeletal , Myoblasts , Oxidative PhosphorylationABSTRACT
PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.
Subject(s)
Humans , Acidosis, Lactic , Classification , Creatine Kinase , Diagnosis , DNA, Mitochondrial , Electron Transport , Enzyme Assays , Gastrointestinal Motility , Gastrointestinal Tract , Genes, vif , Kearns-Sayre Syndrome , Magnetic Resonance Imaging , Mitochondrial Diseases , Muscles , Muscular Diseases , Ophthalmoplegia , Ophthalmoplegia, Chronic Progressive External , Prevalence , Retinitis Pigmentosa , Retrospective StudiesABSTRACT
The present study investigated the effect of different frequencies (three and five times a week) on electron transport chain and oxidative stress after 8 weeks of run training. Methods: Eighteen male mice (CF1, 30-35g) were distributed into the following groups (n=6): untrained (UT); trained three-time per week (T3) and trained five- time per week (T5). All training sessions were at the same intensity and duration (45min/day) in a treadmill for small animals. Forty-eight hours after the last training session, the animals were killed by decapitation and quadriceps (red portion) was removed and stored at -70ºC. Succinate dehydrogenase (SDH), complexes I, II, II-III, IV and hydroperoxides were measured. Results: Training sessions for five times per week were more effective in increasing the mitochondrial respiratory chain enzyme activities (SDH, complexes I, II, II-III, IV) as well as in decreasing the formation hydroperoxides than sessions performed for three times training per week (p<0.05). Conclusion: Our findings clearly showed that a higher the frequency of training session promotes a greater activity of the electron transport chain and consequently reduces the oxidative stress in healthy animals.(AU)
Subject(s)
Animals , Male , Rats , Muscle Development/physiology , Oxidative Stress , Electron Transport/physiologyABSTRACT
ABSTRACT Bioelectrochemistry can be defined as a branch of Chemical Science concerned with electron-proton transfer and transport involving biomolecules, as well as electrode reactions of redox enzymes. The bioelectrochemical reactions and system have direct impact in biotechnological development, in medical devices designing, in the behavior of DNA-protein complexes, in green-energy and bioenergy concepts, and make it possible an understanding of metabolism of all living organisms (e.g. humans) where biomolecules are integral to health and proper functioning. In the last years, many researchers have dedicated itself to study different redox enzymes by using electrochemistry, aiming to understand their mechanisms and to develop promising bioanodes and biocathodes for biofuel cells as well as to develop biosensors and implantable bioelectronics devices. Inside this scope, this review try to introduce and contemplate some relevant topics for enzyme bioelectrochemistry, such as the immobilization of the enzymes at electrode surfaces, the electron transfer, the bioelectrocatalysis, and new techniques conjugated with electrochemistry vising understand the kinetics and thermodynamics of redox proteins. Furthermore, examples of recent approaches in designing biosensors and biofuel developed are presented.
Subject(s)
Bioelectric Energy Sources , Biosensing Techniques , Electrochemistry , Electron Transport , Enzymes/chemistry , Enzymes/physiologyABSTRACT
BACKGROUND AND PURPOSE: The pathogenesis of mitochondrial disease (MD) involves the disruption of cellular energy metabolism, which results from defects in the mitochondrial respiratory chain complex (MRC). We investigated whether infants with MRC I defects showed ultrastructural changes in skeletal muscle. METHODS: Twelve infants were enrolled in this study. They were initially evaluated for unexplained neurodegenerative symptoms, myopathies, or other progressive multiorgan involvement, and underwent muscle biopsies when MD was suspected. Muscle tissue samples were subjected to biochemical enzyme assays and observation by transmission electron microscopy. We compared and analyzed the ultrastructure of skeletal muscle tissues obtained from patients with and without MRC I defects. RESULTS: Biochemical enzyme assays confirmed the presence of MRC I defects in 7 of the 12 patients. Larger mitochondria, lipid droplets, and fused structures between the outer mitochondrial membrane and lipid droplets were observed in the skeletal muscles of patients with MRC I defects. CONCLUSIONS: Mitochondrial functional defects in MRC I disrupt certain activities related to adenosine triphosphate synthesis that produce changes in the skeletal muscle. The ultrastructural changes observed in the infants in this study might serve as unique markers for the detection of MD.
Subject(s)
Humans , Infant , Adenosine Triphosphate , Biopsy , Electron Transport , Energy Metabolism , Enzyme Assays , Lipid Droplets , Microscopy, Electron, Transmission , Mitochondria , Mitochondrial Diseases , Mitochondrial Membranes , Muscle, Skeletal , Muscular DiseasesABSTRACT
Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined. Compared to non-tumor tissues, UQCRB gene expression was upregulated in CRC tissues. Gene and protein expression of the genes were positively correlated. Copy number variation (CNV) differences in UQCRB were observed in CRC tissues (1.32-fold) compared to non-tumor tissues. The CNV of UQCRB in CRC tissues increased proportionally with gene expression and clinical stage. Single-nucleotide polymorphisms in the 3′-untranslated region of UQCRB (rs7836698 and rs10504961) were investigated, and the rs7836698 polymorphism was associated with CRC clinical stage. DNA methylation of the UQCRB promoter revealed that most CRC patients had high methylation levels (12/15 patients) in CRC tissues compared to non-tumor tissues. UQCRB overexpression and CNV gain were correlated with specific CRC clinico-pathological features, indicating clinical significance as a prognostic predictor in CRC. Gene structural factors may be more important than gene transcription repression factors with respect to DNA methylation in UQCRB overexpression. Our results provide novel insights into the critical role of UQCRB in regulating CRC, supporting UQCRB as a new candidate for the development of diagnostics for CRC patients.