Displaying publications 1 - 20 of 36 in total

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  1. Mitochondria and diabetes: insights and potential therapies
    Moorthy R, Bhattamisra SK, Pandey M, Mayuren J, Kow CS, Candasamy M
    Expert Rev Endocrinol Metab, 2024 Mar;19(2):141-154.
    PMID: 38347803 DOI: 10.1080/17446651.2024.2307526
    INTRODUCTION: Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney dysfunction, and cancer. The current review explores the crucial role of mitochondria, essential for fuel metabolism, in diabetes-related processes.

    AREAS COVERED: Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.

    EXPERT OPINION: MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.

    Matched MeSH terms: Mitochondria/genetics
  2. Signatures of purifying selection and site-specific positive selection on the mitochondrial DNA of dromedary camels (Camelus dromedarius)
    Bahbahani H, Al-Zoubi S, Ali F, Afana A, Dashti M, Al-Ateeqi A, et al.
    Mitochondrion, 2023 Mar;69:36-42.
    PMID: 36690316 DOI: 10.1016/j.mito.2023.01.004
    The two species of the Old World Camelini tribe, dromedary and Bactrian camels, show superior adaptability to the different environmental conditions they populate, e.g. desert, mountains and coastal areas, which might be associated with adaptive variations on their mitochondrial DNA. Here, we investigate signatures of natural selection in the 13-mitochondrial protein-coding genes of different dromedary camel populations from the Arabian Peninsula, Africa and southwest Asia. The full mitogenome sequences of 42 dromedaries, 38 domestic Bactrian, 29 wild Bactrian camels and 31 samples representing the New World Lamini tribe reveal species-wise genetic distinction among Camelidae family species, with no evidence of geographic distinction among dromedary camels. We observe gene-wide signals of adaptive divergence between the Old World and New World camels, with evidence of purifying selection among Old World camel species. Upon comparing the different Camelidae tribes, 27 amino acid substitutions across ten mtDNA protein-coding genes were found to be under positive selection, in which, 24 codons were defined to be under positive adaptive divergence between Old World and New World camels. Seven codons belonging to three genes demonstrated positive selection in dromedary lineage. A total of 89 codons were found to be under positive selection in Camelidae family based on investigating the impact of amino acid replacement on the physiochemical properties of proteins, including equilibrium constant and surrounding hydrophobicity. These mtDNA variants under positive selection in the Camelidae family might be associated with their adaptation to their contrasting environments.
    Matched MeSH terms: Mitochondria/genetics
  3. Fulltext Changes in Mitochondrial Epigenome in Type 2 Diabetes Mellitus
    Low HC, Chilian WM, Ratnam W, Karupaiah T, Md Noh MF, Mansor F, et al.
    Br J Biomed Sci, 2023;80:10884.
    PMID: 36866104 DOI: 10.3389/bjbs.2023.10884
    Type 2 Diabetes Mellitus is a major chronic metabolic disorder in public health. Due to mitochondria's indispensable role in the body, its dysfunction has been implicated in the development and progression of multiple diseases, including Type 2 Diabetes mellitus. Thus, factors that can regulate mitochondrial function, like mtDNA methylation, are of significant interest in managing T2DM. In this paper, the overview of epigenetics and the mechanism of nuclear and mitochondrial DNA methylation were briefly discussed, followed by other mitochondrial epigenetics. Subsequently, the association between mtDNA methylation with T2DM and the challenges of mtDNA methylation studies were also reviewed. This review will aid in understanding the impact of mtDNA methylation on T2DM and future advancements in T2DM treatment.
    Matched MeSH terms: Mitochondria/genetics
  4. Fulltext Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement
    Kaiyrzhanov R, Mohammed SEM, Maroofian R, Husain RA, Catania A, Torraco A, et al.
    Am J Hum Genet, 2022 Sep 01;109(9):1692-1712.
    PMID: 36055214 DOI: 10.1016/j.ajhg.2022.07.007
    Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K+/H+ exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K+ efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial pathologies.
    Matched MeSH terms: Mitochondria/genetics
  5. Somatic mitochondrial DNA mutations in different grades of glioma
    Soon BH, Abu N, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, et al.
    Per Med, 2022 01;19(1):25-39.
    PMID: 34873928 DOI: 10.2217/pme-2021-0033
    Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
    Matched MeSH terms: Mitochondria/genetics
  6. Fulltext Whole mitochondrial genome sequencing of Malaysian patients with cardiomyopathy
    Kuan SW, Chua KH, Tan EW, Tan LK, Loch A, Kee BP
    PeerJ, 2022;10:e13265.
    PMID: 35441061 DOI: 10.7717/peerj.13265
    Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.
    Matched MeSH terms: Mitochondria/genetics
  7. Fulltext Mitochondrial marker implies fishery separate management units for spotted sardinella, Amblygaster sirm (Walbaum, 1792) populations in the South China Sea and the Andaman Sea
    Jamaludin NA, Jamaluddin JAF, Rahim MA, Mohammed Akib NA, Ratmuangkhwang S, Mohd Arshaad W, et al.
    PeerJ, 2022;10:e13706.
    PMID: 35860045 DOI: 10.7717/peerj.13706
    The spotted sardinella, Amblygaster sirm (Walbaum, 1792), is a commercial sardine commonly caught in Malaysia. Lack of management of these marine species in Malaysian waters could lead to overfishing and potentially declining fish stock populations. Therefore, sustainable management of this species is of paramount importance to ensure its longevity. As such, molecular information is vital in determining the A. sirm population structure and management strategy. In the present study, mitochondrial DNA Cytochrome b was sequenced from 10 A. sirm populations: the Andaman Sea (AS) (two), South China Sea (SCS) (six), Sulu Sea (SS) (one), and Celebes Sea (CS) (one). Accordingly, the intra-population haplotype diversity (Hd) was high (0.91-1.00), and nucleotide diversity (π) was low (0.002-0.009), which suggests a population bottleneck followed by rapid population growth. Based on the phylogenetic trees, minimum spanning network (MSN), population pairwise comparison, and F ST,and supported by analysis of molecular variance (AMOVA) and spatial analysis of molecular variance (SAMOVA) tests, distinct genetic structures were observed (7.2% to 7.6% genetic divergence) between populations in the SCS and its neighboring waters, versus those in the AS. Furthermore, the results defined A. sirm stock boundaries and evolutionary between the west and east coast (which shares the same waters as western Borneo) of Peninsular Malaysia. In addition, genetic homogeneity was revealed throughout the SCS, SS, and CS based on the non-significant F STpairwise comparisons. Based on the molecular evidence, separate management strategies may be required for A. sirm of the AS and the SCS, including its neighboring waters.
    Matched MeSH terms: Mitochondria/genetics
  8. Improving the phylogenetic resolution of Malaysian and Javan mahseer (Cyprinidae), Tor tambroides and Tor tambra: Whole mitogenomes sequencing, phylogeny and potential mitogenome markers
    Lim LWK, Chung HH, Lau MML, Aziz F, Gan HM
    Gene, 2021 Jul 30;791:145708.
    PMID: 33984441 DOI: 10.1016/j.gene.2021.145708
    The true mahseer (Tor spp.) is one of the highest valued fish in the world due to its high nutritional value and great unique taste. Nevertheless, its morphological characterization and single mitochondrial gene phylogeny in the past had yet to resolve the ambiguity in its taxonomical classification. In this study, we sequenced and assembled 11 complete mahseer mitogenomes collected from Java of Indonesia, Pahang and Terengganu of Peninsular Malaysia as well as Sarawak of East Malaysia. The mitogenome evolutionary relationships among closely related Tor spp. samples were investigated based on maximum likelihood phylogenetic tree construction. Compared to the commonly used COX1 gene fragment, the complete COX1, Cytb, ND2, ND4 and ND5 genes appear to be better phylogenetic markers for genetic differentiation at the population level. In addition, a total of six population-specific mitolineage haplotypes were identified among the mahseer samples analyzed, which this offers hints towards its taxonomical landscape.
    Matched MeSH terms: Mitochondria/genetics
  9. Fulltext Accumulation of Mitochondrial DNA Microsatellite Instability in Malaysian Patients with Primary Central Nervous System Tumors
    Radzak S, Khair Z, Ahmad F, Idris Z, Yusoff A
    Turk Neurosurg, 2021;31(1):99-106.
    PMID: 33491172 DOI: 10.5137/1019-5149.JTN.27893-20.4
    AIM: To determine the mitochondrial microsatellite instability (mtMSI) status in a series of Malaysian patients with brain tumors. Furthermore, we analyzed whether the mtMSI status is associated with the clinicopathological features of the patients.

    MATERIAL AND METHODS: Forty fresh frozen tumor tissues along with blood samples of brain tumor patients were analyzed for mtMSI by PCR amplification of genomic DNAs, and the amplicons were directly sequenced in both directions using Sanger sequencing.

    RESULTS: Microsatellite analysis revealed that 20% (8 out of 40) of the tumors were mtMSI positive with a total of 8 mtMSI changes. All mtMSI markers were detected in D310 and D16184 of the D-loop region. Additionally, no significant association was observed between mtMSI status and clinicopathological features.

    CONCLUSION: The variations, specifically the mtMSI, suggest that the mitochondrial DNA (mtDNA) can be targeted for genomic alteration in brain tumors. Therefore, the specific role of mtDNA alteration in brain tumor development and prognosis requires further investigation.

    Matched MeSH terms: Mitochondria/genetics
  10. Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages
    Tham YY, Choo QC, Muhammad TST, Chew CH
    Mol Biol Rep, 2020 Dec;47(12):9595-9607.
    PMID: 33259010 DOI: 10.1007/s11033-020-06019-9
    Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the pathogenesis of insulin resistance. Lauric acid is a 12-carbon medium chain fatty acid (MCFA) found abundantly in coconut oil or palm kernel oil and it comes with multiple beneficial effects. This research objective was to uncover the effects of the lauric acid on glucose uptake, mitochondrial function and mitochondrial biogenesis in insulin-resistant macrophages. THP-1 monocytes were differentiated into macrophages and induce insulin resistance, before they were treated with increasing doses of lauric acid (5 μM, 10 μM, 20 μM, and 50 μM). Glucose uptake assay, cellular ROS and ATP production assays, mitochondrial content and membrane potential assay were carried out to analyse the effects of lauric acid on insulin resistance and mitochondrial biogenesis in the macrophages. Quantitative RT-PCR (qRT-PCR) and western blot analysis were also performed to determine the expression of the key regulators. Insulin-resistant macrophages showed lower glucose uptake, GLUT-1 and GLUT-3 expression, and increased hallmarks of mitochondrial dysfunction. Interestingly, lauric acid treatment upregulated glucose uptake, GLUT-1 and GLUT-3 expressions. The treatment also restored the mitochondrial biogenesis in the insulin-resistant macrophages by improving ATP production, oxygen consumption, mitochondrial content and potential, while it promoted the expression of mitochondrial biogenesis regulator genes such as TFAM, PGC-1α and PPAR-γ. We show here that lauric acid has the potential to improve insulin sensitivity and mitochondrial dysregulation in insulin-resistant macrophages.
    Matched MeSH terms: Mitochondria/genetics
  11. Fulltext Mitochondrial DNA alterations may influence the cisplatin responsiveness of oral squamous cell carcinoma
    Aminuddin A, Ng PY, Leong CO, Chua EW
    Sci Rep, 2020 May 12;10(1):7885.
    PMID: 32398775 DOI: 10.1038/s41598-020-64664-3
    Cisplatin is the first-line chemotherapeutic agent for the treatment of oral squamous cell carcinoma (OSCC). However, the intrinsic or acquired resistance against cisplatin remains a major obstacle to treatment efficacy in OSCC. Recently, mitochondrial DNA (mtDNA) alterations have been reported in a variety of cancers. However, the role of mtDNA alterations in OSCC has not been comprehensively studied. In this study, we evaluated the correlation between mtDNA alterations (mtDNA content, point mutations, large-scale deletions, and methylation status) and cisplatin sensitivity using two OSCC cell lines, namely SAS and H103, and stem cell-like tumour spheres derived from SAS. By microarray analysis, we found that the tumour spheres profited from aberrant lipid and glucose metabolism and became resistant to cisplatin. By qPCR analysis, we found that the cells with less mtDNA were less responsive to cisplatin (H103 and the tumour spheres). Based on the findings, we theorised that the metabolic changes in the tumour spheres probably resulted in mtDNA depletion, as the cells suppressed mitochondrial respiration and switched to an alternative mode of energy production, i.e. glycolysis. Then, to ascertain the origin of the variation in mtDNA content, we used MinION, a nanopore sequencer, to sequence the mitochondrial genomes of H103, SAS, and the tumour spheres. We found that the lower cisplatin sensitivity of H103 could have been caused by a constellation of genetic and epigenetic changes in its mitochondrial genome. Future work may look into how changes in mtDNA translate into an impact on cell function and therefore cisplatin response.
    Matched MeSH terms: Mitochondria/genetics
  12. Activation of death receptor, DR5 and mitochondria-mediated apoptosis by a 3,4,5-trimethoxybenzyloxy derivative in wild-type and p53 mutant colorectal cancer cell lines
    Chan ZCK, Leong KH, Kareem HS, Norazit A, Noor SM, Ariffin A
    Naunyn Schmiedebergs Arch Pharmacol, 2020 03;393(3):405-417.
    PMID: 31641820 DOI: 10.1007/s00210-019-01730-2
    The rationale of designing compounds containing a (3,4,5-trimethoxybenzyloxy) phenyl moiety is largely due to its potential antioxidant and cytotoxic activities. A previous study focused on its antioxidant mechanism, whereas in this study, we investigated the cytotoxicity of a series of 28 analogues and the mechanism of apoptosis of the most cytotoxic compound against wild-type (HCT-116) and p53 mutant (HT-29) colorectal cancer cell lines. The series of analogues comprise of different families, namely hydrazone, oxadiazole, thiosemicarbazides and triazoles. In the initial cytotoxicity screening, N-(3,4,5-trimethoxybenzylidene)-4-(3,4,5-trimethoxybenzyloxy) benzohydrazide, henceforth known as, P5H, was found to be most cytotoxic against human colorectal cancer cell lines (IC50 for HCT-116 = 11.79 μM and HT-29 = 18.52 μM). Additionally, P5H was found to have some degree of selectivity towards cancer cells compared to normal human colon cells (CCD-112 CoN). Subsequent investigation had brought insight on P5H ability to induce apoptosis in both HCT-116 and HT-29 cell lines. Cell cycle analysis showed both cell lines were arrested at the G2/M phase upon treatment. Our study concluded that P5H induced the death receptor, DR5 in HCT-116 and mitochondria-mediated apoptosis pathway in HT-29. Therefore, P5H may be a promising candidate as a chemotherapy agent against colon cancer. Graphical abstract The apoptotic pathways induced in HT-29 and HCT-116 cells upon P5H treatment.
    Matched MeSH terms: Mitochondria/genetics
  13. Sequencing and characterization of complete mitogenome DNA of Rasbora tornieri (Cypriniformes: Cyprinidae: Rasbora) and its evolutionary significance
    Chung HH, Anak Kamar CK, Kit Lim LW, Roja JS, Liao Y, Tsan-Yuk Lam T, et al.
    J Genet, 2020;99.
    PMID: 32893838
    The yellowtail rasbora (Rasbora tornieri) is a miniature ray-finned fish categorized under the genus Rasbora in the family of Cyprinidae. In this study, a complete mitogenome sequence of R. tornieri was sequenced using four primers targeting two halves of the mitogenome with overlapping flanking regions. The size of mitogenome was 16,573 bp, housing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organization was detected between this species and other members of Rasbora genus. The heavy strand encompassed 28 genes while the light strand accommodated the other nine genes. Most protein-coding genes execute ATG as start codon, excluding COI and ND3 genes, which utilized GTG instead. The central conserved sequence blocks (CSB-E, CSB-F and CSB-D), variable sequence blocks (CSB-1, CSB-3 and CSB-2) as well as the terminal associated sequence (TAS) were conserved within the control region. The maximum likelihood phylogenetic family tree revealed the divergence of R. tornieri from the basal region of the Rasbora clade, where its evolutionary relationships with other Rasbora members are poorly resolved as indicated by the low bootstrap values. This work acts as window for further population genetics and molecular evolution studies of Rasbora genus in future.
    Matched MeSH terms: Mitochondria/genetics*
  14. Fulltext Comparative mitogenomics of the Decapoda reveals evolutionary heterogeneity in architecture and composition
    Tan MH, Gan HM, Lee YP, Bracken-Grissom H, Chan TY, Miller AD, et al.
    Sci Rep, 2019 Jul 24;9(1):10756.
    PMID: 31341205 DOI: 10.1038/s41598-019-47145-0
    The emergence of cost-effective and rapid sequencing approaches has resulted in an exponential rise in the number of mitogenomes on public databases in recent years, providing greater opportunity for undertaking large-scale comparative genomic and systematic research. Nonetheless, current datasets predominately come from small and disconnected studies on a limited number of related species, introducing sampling biases and impeding research of broad taxonomic relevance. This study contributes 21 crustacean mitogenomes from several under-represented decapod infraorders including Polychelida and Stenopodidea, which are used in combination with 225 mitogenomes available on NCBI to investigate decapod mitogenome diversity and phylogeny. An overview of mitochondrial gene orders (MGOs) reveals a high level of genomic variability within the Decapoda, with a large number of MGOs deviating from the ancestral arthropod ground pattern and unevenly distributed among infraorders. Despite the substantial morphological and ecological variation among decapods, there was limited evidence for correlations between gene rearrangement events and species ecology or lineage specific nucleotide substitution rates. Within a phylogenetic context, predicted scenarios of rearrangements show some MGOs to be informative synapomorphies for some taxonomic groups providing strong independent support for phylogenetic relationships. Additional comparisons for a range of mitogenomic features including nucleotide composition, strand asymmetry, unassigned regions and codon usage indicate several clade-specific trends that are of evolutionary and ecological interest.
    Matched MeSH terms: Mitochondria/genetics*
  15. Fulltext Ageing in Pgc-1β-/- mice modelling mitochondrial dysfunction induces differential expression of a range of genes regulating ventricular electrophysiology
    Edling CE, Fazmin IT, Chadda KR, Ahmad S, Valli H, Grace AA, et al.
    Biosci Rep, 2019 04 30;39(4).
    PMID: 30914453 DOI: 10.1042/BSR20190127
    Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β (Pgc-1β-/- ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with Pgc-1β knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the Pgc-1β-/- ventricular tissue compared with the WT. Although most individual genes are not significantly differentially expressed, a pattern is apparent when the genes are grouped according to their functional properties. Genes encoding proteins relating to ATPase activity, potassium ion channels relating to repolarisation and resting membrane potential, and genes encoding proteins in the cAMP pathway are found to be significantly down-regulated in the Pgc-1β deficient mice. On the contrary, the pacemaker channel genes Hcn3 and Hcn4 are up-regulated in subsets of the Pgc-1β deficient tissue. Furthermore, we found that with age, especially in the Pgc-1β-/- genotype, most genes are up-regulated including genes relating to the resting membrane potential, calcium homeostasis, the cAMP pathway, and most of the tested adrenoceptors. In conclusion, we here demonstrate how a complex pattern of many modest changes at gene level may explain major functional differences of the action potential related to ageing and mitochondrial dysfunction.
    Matched MeSH terms: Mitochondria/genetics
  16. Universal mitochondrial 16s rRNA biomarker for mini-barcode to identify fish species in Malaysian fish products
    Hossain MAM, Uddin SMK, Chowdhury ZZ, Sultana S, Johan MR, Rohman A, et al.
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2019 Apr;36(4):493-506.
    PMID: 30865559 DOI: 10.1080/19440049.2019.1580389
    Mislabelling in fish products is a highly significant emerging issue in world fish trade in terms of health and economic concerns. DNA barcoding is an efficient sequencing-based tool for detecting fish species substitution but due to DNA degradation, it is in many cases difficult to amplify PCR products of the full-length barcode marker (~650 bp), especially in severely processed products. In the present study, a pair of universal primers targeting a 198 bp sequence of the mitochondrial 16s rRNA gene was designed for identification of fish species in the processed fish products commonly consumed in Malaysia. The specificity of the universal primers was tested by both in-silico studies using bioinformatics software and through cross-reaction assessment by practical PCR experiments against the DNA from 38 fish species and 22 other non-target species (animals and plants) and found to be specific for all the tested fish species. To eliminate the possibility of any false-negative detection, eukaryotic endogenous control was used during specificity evaluation. The developed primer set was validated with various heat-treated (boiled, autoclaved and microwaved) fish samples and was found to show high stability under all processing conditions. The newly developed marker successfully identified 92% of the tested commercial fish products with 96-100% sequence similarities. This study reveals a considerable degree of species mislabelling (20.8%); 5 out of 24 fish products were found to be mislabelled. The new marker developed in this work is a reliable tool to identify fish species even in highly processed products and might be useful in detecting fish species substitution thus protecting consumers' health and economic interests.
    Matched MeSH terms: Mitochondria/genetics*
  17. Fulltext Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer's disease, Parkinson's disease
    Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.
    Biomed Pharmacother, 2019 Mar;111:765-777.
    PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101
    Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.
    Matched MeSH terms: Mitochondria/genetics
  18. Attenuation of oxidative stress induced mitochondrial dysfunction and cytotoxicity in fibroblast cells by sulfated polysaccharide from Padina gymnospora
    Vasantharaja R, Stanley Abraham L, Gopinath V, Hariharan D, Smita KM
    Int J Biol Macromol, 2019 Mar 01;124:50-59.
    PMID: 30445094 DOI: 10.1016/j.ijbiomac.2018.11.104
    In this present study, isolation, characterization and protective effect of sulfated polysaccharide (SP) isolated from the brown algae Padina gymnospora was investigated. SP was isolated and characterized through FT-IR, 1H NMR, TGA, GC-MS and CHN analysis. The molecular weight of SP was found to be 16 kDa. The isolated SP contains 29.4 ± 0.35% of sulfate, 27 ± 0.11% of fucose, 0.05 ± 0.12% of protein, respectively. Furthermore, SP exhibits its excellent radical scavenging effects were evaluated by DPPH, ABTS radical scavenging and reducing power assays. Moreover, pretreatment with SP significantly mitigates H2O2 induced cytotoxicity in L-929 cells in a dose dependent manner. Furthermore, SP pretreatment ameliorates oxidative stress induced apoptosis and DNA damage, alleviates the generation of intracellular reactive oxygen species (ROS) and restores mitochondrial membrane potential (MMP) in L-929 cells through its antioxidant potential. Together, these results suggest that SP can be exploited as a natural antioxidant in the food and pharmaceutical industries.
    Matched MeSH terms: Mitochondria/genetics
  19. Phylogeny, historical biogeography, and diversification of angiosperm order Ericales suggest ancient Neotropical and East Asian connections
    Rose JP, Kleist TJ, Löfstrand SD, Drew BT, Schönenberger J, Sytsma KJ
    Mol Phylogenet Evol, 2018 05;122:59-79.
    PMID: 29410353 DOI: 10.1016/j.ympev.2018.01.014
    Inferring interfamilial relationships within the eudicot order Ericales has remained one of the more recalcitrant problems in angiosperm phylogenetics, likely due to a rapid, ancient radiation. As a result, no comprehensive time-calibrated tree or biogeographical analysis of the order has been published. Here, we elucidate phylogenetic relationships within the order and then conduct time-dependent biogeographical and diversification analyses by using a taxon and locus-rich supermatrix approach on one-third of the extant species diversity calibrated with 23 macrofossils and two secondary calibration points. Our results corroborate previous studies and also suggest several new but poorly supported relationships. Newly suggested relationships are: (1) holoparasitic Mitrastemonaceae is sister to Lecythidaceae, (2) the clade formed by Mitrastemonaceae + Lecythidaceae is sister to Ericales excluding balsaminoids, (3) Theaceae is sister to the styracoids + sarracenioids + ericoids, and (4) subfamilial relationships with Ericaceae suggest that Arbutoideae is sister to Monotropoideae and Pyroloideae is sister to all subfamilies excluding Arbutoideae, Enkianthoideae, and Monotropoideae. Our results indicate Ericales began to diversify 110 Mya, within Indo-Malaysia and the Neotropics, with exchange between the two areas and expansion out of Indo-Malaysia becoming an important area in shaping the extant diversity of many families. Rapid cladogenesis occurred along the backbone of the order between 104 and 106 Mya. Jump dispersal is important within the order in the last 30 My, but vicariance is the most important cladogenetic driver of disjunctions at deeper levels of the phylogeny. We detect between 69 and 81 shifts in speciation rate throughout the order, the vast majority of which occurred within the last 30 My. We propose that range shifting may be responsible for older shifts in speciation rate, but more recent shifts may be better explained by morphological innovation.
    Matched MeSH terms: Mitochondria/genetics
  20. Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation, migration and induces apoptosis in human cervical cancer HeLa cells through oxidative stress mediated intrinsic mitochondrial pathway
    Khanam R, Kumar R, Hejazi II, Shahabuddin S, Meena R, Jayant V, et al.
    Apoptosis, 2018 02;23(2):113-131.
    PMID: 29349707 DOI: 10.1007/s10495-018-1439-x
    Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis. Further, we also evaluated oxidative stress generated by these synthetic derivatives (5a-5h). Cell viability studies revealed that among all, the compound N-(3-chloro-2-(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4-phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of HeLa cells in a concentration dependent manner having IC50 value of 29.44 ± 1.46 µg/ml. Morphological changes, colonies suppression and inhibition of migration clearly showed the antineoplasicity in HeLa cells treated with 5e. Simultaneously, phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest showed ongoing apoptosis in the HeLa cancer cells induced by compound 5e in concentration dependent manner. Additionally, generation of intracellular ROS along with the decrease in mitochondrial membrane potential supported that compound 5e caused oxidative stress resulting in apoptosis through mitochondria mediated pathway. Elevation in the level of cytochrome c and upregulation in expression of caspase-3 clearly indicated the involvement of the intrinsic pathway of programmed cell death. In brief; compound 5e could serve as a promising lead for the development of an effective antitumor agent.
    Matched MeSH terms: Mitochondria/genetics
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