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International Journal of Molecular... Dec 2023Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria... (Review)
Review
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from HS and NH. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestinal Mucosa; Mitochondria
PubMed: 38069446
DOI: 10.3390/ijms242317124 -
Frontiers in Bioscience (Landmark... Nov 2023Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases. Moreover, obesity has been shown to cause mitochondrial dysfunction through oxidative stress and inflammation, eventually affecting energy metabolism. However, high-intensity interval training (HIIT) can improve mitochondrial efficiency through exercise-induced mitochondrial adaptations. This systematic review and meta-analysis aims to examine the potential effects of HIIT on mitochondrial-associated indices in obese and overweight adults.
METHODS
PubMed, Scopus, and Web of Science databases were searched.
RESULTS
Twenty-eight eligible studies were included, involving 530 participants. HIIT was found to significantly improve the activity of citrate synthase (CS), cytochrome C (COX-IV), beta-hydroxyacyl CoA-dehydrogenase (β-HAD), Complexes I-V as well as VO2max in overweight and obese individuals, whereas no significant changes were shown in PGC-1α and SIRT1. Interestingly, subgroup analyses revealed that CS, COX-IV, β-HAD, and Complexes I-V activity exhibited a significant improvement only in the healthy subgroup.
CONCLUSIONS
Overall, HIIT can be utilized to enhance mitochondrial-associated indices in overweight and obese individuals. However, this improvement may be health status dependent.
Topics: Adult; Humans; Overweight; High-Intensity Interval Training; Oxygen Consumption; Obesity; Mitochondria
PubMed: 38062841
DOI: 10.31083/j.fbl2811281 -
Frontiers in Physiology 20238-Hydroxy-2'-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue...
8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue healing. The aim of this study is to quantify the 8-OHdG response after a single session of exercise in both trained and untrained adults. A systematic review and meta-analysis of exercise intervention studies measuring changes in blood 8-OHdG following resistance exercise and aerobic exercise were conducted. The literature search included Web of Science, PubMed, BASE, and Scopus, with publications up to February 2023 included. Subgroup analysis of training status was also conducted. Sixteen studies involving 431 participants met the eligibility criteria. Resistance exercise showed a medium effect on increasing circulating 8-OHdG levels (SMD = 0.66, < 0.001), which was similar for both trained and untrained participants. However, studies on aerobic exercise presented mixed results. For trained participants, a small effect of aerobic exercise on increasing circulating 8-OHdG levels was observed (SMD = 0.42; < 0.001). In contrast, for untrained participants, a large effect of decreasing circulating 8-OHdG levels was observed, mostly after long-duration aerobic exercise (SMD = -1.16; < 0.05). Similar to resistance exercise, high-intensity aerobic exercise (5-45 min, ≥75% VO) significantly increased circulating 8-OHdG levels, primarily in trained participants. Pooled results from the studies confirm an increase in circulating 8-OHdG levels after resistance exercise. However, further studies are needed to fully confirm the circulating 8-OHdG response to aerobic exercise. Increases in 8-OHdG after high-intensity aerobic exercise are observed only in trained individuals, implicating its role in training adaptation. : [https://Systematicreview.gov/], identifier [CRD42022324180].
PubMed: 38028771
DOI: 10.3389/fphys.2023.1275867 -
Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
BMC Psychiatry Nov 2023Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have identified alterations in the content of mitochondrial DNA (mtDNA) in peripheral blood and cerebrospinal fluid of individuals with depression. Researchers have sought to establish a clear association between mtDNA and depression. Consequently, we conducted a comprehensive meta-analysis to assess the existing evidence regarding the impact of mtDNA on depression.
METHODS
This study conducted a thorough search of the following databases up to March 13, 2023: PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, the China Science and Technology Journal Database, and China National Knowledge Infrastructure. The meta-analysis was carried out using RevMan (version 5.4) and Stata (version 16.0) software. In addition, publication bias was assessed with funnel plots, Begg's test and Egger's test.
RESULTS
Our analysis included data from 10 articles, including 12 studies for further examination. A total of 1400 participants were included in this study, comprising 709 (including 300 males and 409 females) patients with depression and 691 (including 303 males and 388 females) healthy controls. The average age of depressed patients was (42.98 ± 2.55) years, and the average age of healthy people was (41.71 ± 2.6) years. The scales used to assess outcomes are Hamilton-rating scale for Depression(4 articles), Montgomery-Asberg Depression Rating Scale(3 articles), and Mini-Internatioal Neuropsychiatric Interview (1 articles). The meta-analysis revealed significantly higher levels of mtDNA in circulating blood samples and skin fibroblasts of individuals with depression in comparison to healthy controls [standardized mean difference(SMD) = 0.42, 95% confidence intervals(CI): 0.16, 0.67].
CONCLUSIONS
Our study concludes that there is a significant (p < 0.05) increase in mtDNA levels in serum, plasma, and cerebrospinal fluid in individuals with depression. These findings suggest that mtDNA could serve as a potential biomarker for diagnosing depression.
REGISTRATION NUMBER
PROSPERO CRD42023414285.
Topics: Male; Female; Humans; Adult; Middle Aged; Depression; DNA, Mitochondrial; Risk Factors; Health Status; Mitochondria
PubMed: 37993802
DOI: 10.1186/s12888-023-05358-8 -
Medicine Nov 2023Anti-mitochondrial antibodies (AMA) and the M2 subtype are considered serological hallmarks in the diagnosis of primary biliary cholangitis (PBC). However, these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anti-mitochondrial antibodies (AMA) and the M2 subtype are considered serological hallmarks in the diagnosis of primary biliary cholangitis (PBC). However, these autoantibodies may be undetectable in some patients. This meta-analysis aimed to evaluate the diagnostic accuracy of serum AMA and M2 for PBC.
METHODS
We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were calculated using a random-effects model. We also constructed hierarchical summary receiver operating characteristic curves and calculated the area under the curve values.
RESULTS
Our meta-analysis included 28 studies, of which 24 examined the diagnostic accuracy of AMA for PBC. Pooled sensitivity and specificity of AMA were 84% (95% confidence intervals [CI] 77-90%) and 98% (96-99%), respectively. Pooled LR+, LR-, and DOR were 42.2 (22.1-80.5), 0.16 (0.11-0.24), and 262 (114-601), respectively. Sixteen studies explored the diagnostic value of the M2 subtype, demonstrating pooled sensitivity and specificity of 89% (81-94%) and 96% (93-98%), respectively. Pooled LR+, LR-, and DOR were 20.3 (8.0-51.1), 0.12 (0.05-0.26), and 169 (41-706), respectively. The hierarchical summary receiver operating characteristic curves for both of serum AMA and M2 subtype lie closer to the upper left corner of the plot with area under the curve values of 0.98 (95% CI = 0.96-0.99) and 0.98 (95% CI = 0.96-0.99) respectively.
CONCLUSION
This meta-analysis provides evidence affirming the utility of AMA and M2 as sensitive and specific serological hallmarks that can facilitate early screening and diagnosis of PBC.
Topics: Humans; Liver Cirrhosis, Biliary; Mitochondria; Autoantibodies; Sensitivity and Specificity; ROC Curve
PubMed: 37960792
DOI: 10.1097/MD.0000000000036039 -
Frontiers in Public Health 2023Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of diseases. Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) serves as a central rate-limiting enzyme in NAD synthesis, making it an indispensable health mediator. This meta-analysis examined the effect of exercise training on the expression of iNAMPT in humans.
METHODS
We searched PubMed, Scopus, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies published between the inception of the database and July 5, 2023. Using the common-effect model, evidence for the change in iNAMPT following exercise training was synthesized as Cohen's .
RESULTS
The search yielded five eligible studies. The overall effect size is 0.81, with a 95% confidence interval of 0.55 to 1.07. Therefore, a random adult will have a 71.7% probability that iNAMPT will be up-regulated following exercise training. In general, exercise training resulted in a 1.46-fold increase in iNAMPT. Our probability statistics indicate that subgroups of interest may differ practically. Specifically, there is a 79.3% probability of increased iNAMPT in men, compared to a 69.0% probability in the overall population; young adults have a 75.6% probability of having an increased iNAMPT, whereas aged adults have a 68.7% probability; and, iNAMPT has a 75.1% probability increase after aerobic exercise and a 66.4% probability increase after resistance exercise.
CONCLUSION
Exercise training is effective for increasing iNAMPT levels in skeletal muscles. This essential enzyme regulates not only cellular energetics but also healthspan. Therefore, exercise should be promoted as a natural slow-aging lifestyle.
Topics: Humans; Aging; Exercise; Muscle, Skeletal; NAD; Nicotinamide Phosphoribosyltransferase
PubMed: 37954044
DOI: 10.3389/fpubh.2023.1287421 -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Food Science & Nutrition Sep 2023Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial... (Review)
Review
Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial effects on liver function. However, these results are equivocal. This systematic review and meta-analysis aimed to clarify the effect of coenzyme Q10 supplementation on the serum concentration of liver function enzymes. We searched the online databases using relevant keywords up to April 2022. Randomized clinical trials (RCTs) investigating the effect of CoQ10, compared with a control group, on serum concentrations of liver enzymes were included. We found a significant reduction following supplementation with CoQ10 on serum concentrations of alanine aminotransferase (ALT) based on 15 effect sizes from 13 RCTs (weighted mean difference [WMD] = -5.33 IU/L; 95% CI: -10.63, -0.03; = .04), aspartate aminotransferase (AST) based on 15 effect sizes from 13 RCTs (WMD = -4.91 IU/L; 95% CI: -9.35, -0.47; = .03) and gamma-glutamyl transferase (GGT) based on eight effect sizes from six RCTs (WMD = -8.07 IU/L; 95% CI: -12.82, -3.32; = .001; = 91.6%). However, we found no significant effects of CoQ10 supplementation on alkaline phosphatase concentration (WMD = 1.10 IU/L; 95% CI: -5.98, 8.18; = .76). CoQ10 supplementation significantly improves circulating ALT, AST, and GGT levels; therefore, it might positively affect liver function. Further high-quality RCTs with more extended intervention periods and larger sample sizes are recommended to confirm our results.
PubMed: 37701221
DOI: 10.1002/fsn3.3478 -
Nutrients Aug 2023Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this... (Review)
Review
The Role of Nutrition in the Treatment of Sarcopenia in Old Patients: From Restoration of Mitochondrial Activity to Improvement of Muscle Performance, a Systematic Review.
Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.
Topics: Humans; Aged; Sarcopenia; Muscles; Nutritional Status; Malnutrition; Vitamin D; Vitamins; Amino Acids, Branched-Chain; Mitochondria
PubMed: 37686735
DOI: 10.3390/nu15173703