Displaying publications 21 - 40 of 273 in total

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  1. The complete mitogenome of the Morton Bay bug Thenus orientalis (Lund, 1793) (Crustacea: Decapoda: Scyllaridae) from a cooked sample and a new mitogenome order for the Decapoda
    Tan MH, Gan HM, Lee YP, Austin CM
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016;27(2):1277-8.
    PMID: 25103440 DOI: 10.3109/19401736.2014.945554
    The mitochondrial genome sequence of the Morton Bay bug, Thenus orientalis, is documented, which makes it the second mitogenome for species of the family Scyllaridae and the ninth for members of the superfamily Palinuroidae. Thenus orientalis has a mitogenome of 16,826 base pairs consisting of 13 protein-coding genes, 2 ribosomal subunit genes, 23 transfer RNAs, and a non-coding AT-rich region. The base composition of the T. orientalis mitogenome is 31.31% for T, 23.77% for C, 31.05% for A, and 13.87% for G, with an AT bias of 62.36%. In addition to a duplicated trnS1 and several other tRNA gene rearrangements, the mitogenome gene order has novel protein coding gene order with the nad6 and cob genes translocated as a block to a location downstream of the nad3 gene.
    Matched MeSH terms: Mitochondria/genetics; Genome, Mitochondrial*
  2. The complete mitogenome of the swimming crab Thalamita crenata (Rüppell, 1830) (Crustacea; Decapoda; Portunidae)
    Tan MH, Gan HM, Lee YP, Austin CM
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016;27(2):1275-6.
    PMID: 25090400 DOI: 10.3109/19401736.2014.945553
    The complete mitochondrial genome of the swimming crab Thalamita crenata was obtained from a partial genome scan using the MiSeq sequencing system. The Thalamita crenata mitogenome has 15,787 base pairs (70% A+T content) made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a putative 897 bp non-coding AT-rich region. This Thalamita mitogenome sequence is the first for the genus and the eighth for the family Portunidae.
    Matched MeSH terms: Mitochondria/genetics; Genome, Mitochondrial*
  3. Fulltext Phylogenetic relationships of Malaysian monkeys, Cercopithecidae, based on mitochondrial cytochrome c sequences
    Md-Zain BM, Mohamad M, Ernie-Muneerah MA, Ampeng A, Jasmi A, Lakim M, et al.
    Genet. Mol. Res., 2010;9(4):1987-96.
    PMID: 20927717 DOI: 10.4238/vol9-4gmr942
    Mitochondrial DNA cytochrome c oxidase II (COII) gene sequences of Malaysian Cercopithecidae were examined to ascertain their phylogenetic relationships. Colobinae were represented by the genera Presbytis, Trachypithecus and Nasalis, while the genus Macaca represented Cercopithecinae. DNA amplification and sequencing of the COII gene was performed on 16 samples. Symphalangus syndactylus (Hylobatidae) was used as the outgroup. Data were analyzed using both character (maximum parsimony) and distance (neighbor-joining) methods. Tree topologies indicated that Colobinae and Cercopithecinae have their own distinct monophyletic clade. This result was well supported by bootstrap values and genetic distances derived from the Kimura-2-parameter algorithm. Separation of Macaca nemestrina from M. fascicularis was also well supported by bootstrap values. In addition, tree topologies indicate a good resolution of the Colobinae phylogenetic relationships at the intergeneric level, but with low bootstrap support. The position of Nasalis remained problematic in both trees. Overall, COII is a good gene candidate for portraying the phylogenetic relationships of Malaysian primates at the inter- and intra-subfamily levels.
    Matched MeSH terms: Mitochondria/enzymology*
  4. Fulltext The link between Mitochondria and Sarcopenia
    Kamarulzaman NT, Makpol S
    J Physiol Biochem, 2025 Feb;81(1):1-20.
    PMID: 39969761 DOI: 10.1007/s13105-024-01062-7
    Sarcopenia, a widespread condition, is characterized by a variety of factors influencing its development. The causes of sarcopenia differ depending on the age of the individual. It is defined as the combination of decreased muscle mass and impaired muscle function, primarily observed in association with ageing. As people age from 20 to 80 years old, there is an approximate 30% reduction in muscle mass and a 20% decline in cross-sectional area. This decline is attributed to a decrease in the size and number of muscle fibres. The regression of muscle mass and strength increases the risk of fractures, frailty, reduced quality of life, and loss of independence. Muscle cells, fibres, and tissues shrink, resulting in diminished muscle power, volume, and strength in major muscle groups. One prominent theory of cellular ageing posits a strong positive relationship between age and oxidative damage. Heightened oxidative stress leads to early-onset sarcopenia, characterized by neuromuscular innervation breakdown, muscle atrophy, and dysfunctional mitochondrial muscles. Ageing muscles generate more reactive oxygen species (ROS), and experience decreased oxygen consumption and ATP synthesis compared to younger muscles. Additionally, changes in mitochondrial protein interactions, cristae structure, and networks may contribute to ADP insensitivity, which ultimately leads to sarcopenia. Within this framework, this review provides a comprehensive summary of our current understanding of the role of mitochondria in sarcopenia and other muscle degenerative diseases, highlighting the crucial need for further research in these areas.
    Matched MeSH terms: Mitochondria/metabolism
  5. Fulltext Karyotypic and mtDNA based characterization of Malaysian water buffalo
    Shaari N'AL, Jaoi-Edward M, Loo SS, Salisi MS, Yusoff R, Ab Ghani NI, et al.
    BMC Genet, 2019 03 25;20(1):37.
    PMID: 30909863 DOI: 10.1186/s12863-019-0741-0
    BACKGROUND: In Malaysia, the domestic water buffaloes (Bubalus bubalis) are classified into the swamp and the murrah buffaloes. Identification of these buffaloes is usually made via their phenotypic appearances. This study characterizes the subspecies of water buffaloes using karyotype, molecular and phylogenetic analyses. Blood of 105 buffaloes, phenotypically identified as swamp, murrah and crossbred buffaloes were cultured, terminated and harvested using conventional karyotype protocol to determine the number of chromosomes. Then, the D-loop of mitochondrial DNA of 10 swamp, 6 crossbred and 4 murrah buffaloes which were identified earlier by karyotyping were used to construct a phylogenetic tree was constructed.

    RESULTS: Karyotypic analysis confirmed that all 93 animals phenotypically identified as swamp buffaloes with 48 chromosomes, all 7 as crossbreds with 49 chromosomes, and all 5 as murrah buffaloes with 50 chromosomes. The D-loop of mitochondrial DNA analysis showed that 10 haplotypes were observed with haplotype diversity of 0.8000 ± 0.089. Sequence characterization revealed 72 variables sites in which 67 were parsimony informative sites with sequence diversity of 0.01906. The swamp and murrah buffaloes clearly formed 2 different clades in the phylogenetic tree, indicating clear maternal divergence from each other. The crossbreds were grouped within the swamp buffalo clade, indicating the dominant maternal swamp buffalo gene in the crossbreds.

    CONCLUSION: Thus, the karyotyping could be used to differentiate the water buffaloes while genotypic analysis could be used to characterize the water buffaloes and their crossbreds.

    Matched MeSH terms: DNA, Mitochondrial; Mitochondria
  6. Fulltext Revisiting Mitochondria Scored Cancer Progression and Metastasis
    Gundamaraju R, Lu W, Manikam R
    Cancers (Basel), 2021 Jan 23;13(3).
    PMID: 33498743 DOI: 10.3390/cancers13030432
    The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion's instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.
    Matched MeSH terms: Mitochondria
  7. Morphological alteration in mitochondria following diclofenac and ibuprofen administration
    Moorthy M, Fakurazi S, Ithnin H
    Pak J Biol Sci, 2008 Aug 01;11(15):1901-8.
    PMID: 18983031
    This study was conducted to identify and to compare the mitochondrial morphological alterations in livers of rats treated with various doses of diclofenac and ibuprofen. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg(-1) diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every 3 days until day 15. While 200 mg kg(-1) diclofenac and ibuprofen-treated rats (n = 4) were euthanized 10 h posttreatment. The livers were removed, cleaned and a section across the right lobe was taken and fixed in 4% (v/v) glutaraldehyde for electron microscopy analysis and the remaining samples were kept at -80 degrees C for Western blot analysis. Five milligram per kilogram and 10 mg kg(-1) diclofenac-administered rats for 15 days revealed the presence of enlarged mitochondria, irregular and ruptured mitochondrial membranes. While rats administered with 10 mg kg(-1) ibuprofen also showed the presence of mitochondria with irregular membrane structure and ruptured membranes. Western blotting analysis of mitochondrial fractions revealed the expression of cytochrome c in all samples and complete absence of cytochrome c expression in the cytosolic fraction of all samples after day 15. Analysis in 200 mg kg(-1) diclofenac and ibuprofen-treated groups, revealed expression of cytochrome c in both mitochondrial and cytosolic fractions. This observation indicates that both diclofenac and ibuprofen may alter the morphology of mitochondria, leading to cytochrome c release into the cytosol. Further studies needs to be conducted to investigate on the activity of the mitochondria following both treatments.
    Matched MeSH terms: Mitochondria/drug effects*; Mitochondria/enzymology; Mitochondria/ultrastructure
  8. Fulltext Pachyseris inattesa sp. n. (Cnidaria, Anthozoa, Scleractinia): a new reef coral species from the Red Sea and its phylogenetic relationships
    Terraneo TI, Berumen ML, Arrigoni R, Waheed Z, Bouwmeester J, Caragnano A, et al.
    Zookeys, 2014.
    PMID: 25152672 DOI: 10.3897/zookeys.433.8036
    A new scleractinian coral species, Pachyseris inattesa sp. n., is described from the Red Sea. Despite a superficial resemblance with some species in the agariciid genus Leptoseris with which it has been previously confused, P. inattesa sp. n. has micro-morphological characters typical of the genus Pachyseris. This genus, once part of the Agariciidae, is comprised of five extant species and is widely distributed throughout the tropical Indo-Pacific. It is currently incertae sedis as a result of recent molecular analysis and appears to be closely related to the Euphylliidae. A molecular phylogenetic reconstruction including P. inattesa sp. n., the genus type species P. rugosa, and P. speciosa, all present in the Red Sea, was performed using the mitochondrial intergenic spacer between COI and 16S-rRNA. The results confirm that P. inattesa sp. n. is a monophyletic lineage closely related to the other Pachyseris species examined.
    Matched MeSH terms: Mitochondria
  9. Fulltext Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model
    Kehinde SA, Olajide AT, Fatokun TP, Fouad D, Hadi NR, Elgazzar AM, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2025 Mar;398(3):2833-2843.
    PMID: 39287675 DOI: 10.1007/s00210-024-03454-4
    Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P 
    Matched MeSH terms: Mitochondria, Heart/drug effects; Mitochondria, Heart/metabolism; Mitochondria, Heart/pathology
  10. Dexamethasone provoked mitochondrial perturbations in thymus: Possible role of N-acetylglucosamine in restoration of mitochondrial function
    Venugopalan SK, T S S, V N, S M M, S R
    Biomed Pharmacother, 2016 Oct;83:1485-1492.
    PMID: 27619103 DOI: 10.1016/j.biopha.2016.08.068
    Thymus mitochondria play a crucial role in immune function. This study identifies the novel protective role of N-Acetylglucosamine (NAG) in dexamethasone (DEX) induced mitochondrial perturbations in mice thymus. Mice were induced with DEX (5mg/kg) and treated with NAG i.p. (266μg/kg, 400μg/kg and 800μg/kg) for 14 days, Withanolide A (800μg/kg) has been used as positive control. Dose dependent treatment of NAG against DEX significantly restored the mitochondrial enzyme levels (ICDH, KDH, SDH and MDH) and elevated the mitochondrial glutathione antioxidants defense (GSH, SOD, GPX and GST) thus improving the ATP status which was confirmed by ultrastructural alterations in mitochondria and nucleus using TEM studies. Further histopathological studies also revealed that NAG attenuate DEX induced thymotoxicity. Finally, the study concludes that dose dependent treatment of NAG supports a potential role in preventing DEX induced thymotoxicity and NAG acts as a beneficial pharmacological intervention in the DEX induced thymic repercussions.
    Matched MeSH terms: Mitochondria/drug effects*; Mitochondria/metabolism*
  11. Fulltext Rosamines targeting the cancer oxidative phosphorylation pathway
    Lim SH, Wu L, Kiew LV, Chung LY, Burgess K, Lee HB
    PLoS One, 2014;9(3):e82934.
    PMID: 24622277 DOI: 10.1371/journal.pone.0082934
    Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism
  12. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts
    Amini E, Rezaei M, Mohamed Ibrahim N, Golpich M, Ghasemi R, Mohamed Z, et al.
    Mol Neurobiol, 2015 Aug;52(1):492-513.
    PMID: 25195699 DOI: 10.1007/s12035-014-8876-5
    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism
  13. Antioxidant modulation in restoring mitochondrial function in neurodegeneration
    Pahrudin Arrozi A, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Makpol S
    Int J Neurosci, 2017 Mar;127(3):218-235.
    PMID: 27074540 DOI: 10.1080/00207454.2016.1178261
    Alzheimer's disease (AD) and Parkinson's disease (PD) are the leading causes of disability associated with neurodegeneration worldwide. These diseases are influenced by multiple genetic and environmental factors and share similar mechanisms as both are characterized by accumulation and aggregation of misfolded proteins - amyloid-beta (Aβ) in AD and α-synuclein in PD. Over the past decade, increasing evidence has shown that mitochondrial dysfunction and the generation of reactive oxygen species (ROS) are involved in the pathology of these diseases, and the contributions of these defects to the cellular and molecular changes that eventually cause neuronal death have been explored. Using mitochondrial protective agents, such as antioxidants, to combat ROS provides a new strategy for neurodegenerative treatment. In this review, we highlight the potential of multiple types of antioxidants, including vitamins, phytochemicals, fatty acids and minerals, as well as synthetic antioxidants specifically targeting the mitochondria, which can restore mitochondrial function, in the treatment of neurodegenerative disorders at both the pre-clinical and clinical stages by focusing on AD and PD.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism; Mitochondrial Diseases/drug therapy*; Mitochondrial Diseases/etiology*
  14. Regulating Mitochondrial Biogenesis: from Herbal Remedies to Phytomedicine for Cancer Prevention
    Jothy SL, Vijayarathna S, Chen Y, Kanwar JR, Sasidharan S
    Asian Pac J Cancer Prev, 2015;16(17):8015.
    PMID: 26625835
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/physiology*
  15. Targeting glucose metabolism with dichloroacetate (DCA) reduces zika virus replication in brain cortical progenitors at different stages of maturation
    Gilbert-Jaramillo J, Komarasamy TV, Balasubramaniam VR, Heather LC, James WS
    Antiviral Res, 2024 Aug;228:105933.
    PMID: 38851593 DOI: 10.1016/j.antiviral.2024.105933
    The underlying threat of new Zika virus (ZIKV) outbreaks remains, as no vaccines or therapies have yet been developed. In vitro research has shown that glycolysis is a key factor to enable sustained ZIKV replication in neuroprogenitors. However, neither in vivo nor clinical investigation of glycolytic modulators as potential therapeutics for ZIKV-related fetal abnormalities has been conducted. Accordingly, we tested the therapeutic potential of metabolic modulators in relevant in vitro systems comprising two pools of neuroprogenitors (NPCs), which resemble early and late stages of pregnancy. Effective doses of metabolic modulators [3.0 μM] dimethyl fumarate (DMF), [3.2 mM] dichloroacetate (DCA), and [6.3 μM] VER-246608 were determined for these cells by their effect on lactate release, pyruvate dehydrogenase (PDH) activity and cell survival. The drugs were used in a 24h pre-treatment and kept throughout ZIKV infection of NPCs. Drug effects and ZIKV replication were assessed at 24- and 56-h post-infection. In early NPCs treated with DMF, DCA and VER-246608, there was a significant reduction in the extracellular release of ZIKV potentially by PDH-mediated increased mitochondrial oxidation of glucose. Out of the three drugs, only DCA was observed to reduce viral replication in late NPCs treated with DCA. Altogether, our findings suggest that reduction of anaerobic glycolysis could be of therapeutic potential against ZIKV-related fetal abnormalities and that clinical translation should consider the use of specific glycolytic modulators over different trimesters.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism
  16. Fulltext Zamzam Water in Cancer and Beyond: Preclinical Cellular Effects and Proposed Mechanistic Hypotheses
    Hossain MS, Parvez A, Islam MT, Ahmmed S, Hasan MH, Indrayudha P, et al.
    Int J Mol Sci, 2026 Oct 20;27(20).
    PMID: 42942077 DOI: 10.3390/ijms27209308
    Zamzam water (ZW), a naturally occurring alkaline mineral water with a distinctive ionic and trace-element composition, has attracted growing scientific interest due to its reported pharmacological properties and emerging biological effects relevant to cancer research. This review provides a comprehensive mechanistic synthesis that links the physicochemical characteristics of ZW to molecular and cellular processes implicated in cancer biology. Integrating evidence from cancer biology, redox pharmacology, mitochondrial physiology, and cellular signaling, this review examines how the unique mineral composition and mildly alkaline pH of ZW may collectively influence pathways associated with the hallmarks of cancer. Preclinical studies demonstrate context-dependent modulation of cell proliferation, apoptosis, oxidative stress, mitochondrial function, cell-cycle progression, and signaling pathways, including mitogen-activated protein kinase (MAPK) and cyclic AMP (cAMP) networks, across multiple cancer models. Beyond its reported antiproliferative activity, ZW also exhibits antioxidant, anti-inflammatory, and organ-protective effects in non-malignant systems. Importantly, this review proposes a conceptual framework for investigating the relative contributions of mineral ions, ionic homeostasis, redox regulation, and physicochemical properties to the biological effects of ZW, and identifies key mechanistic and methodological gaps. ZW has exhibited cancer-associated biological effects in experimental animals; however, its therapeutic effectiveness has yet to be validated. Future studies integrating standardized physicochemical characterization, molecular validation, multi-omics approaches, and clinical investigations are required to establish its translational relevance in complementary oncology.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism
  17. 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; Mitochondria/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism
  18. Phenylpropanoids isolated from Piper sarmentosum Roxb. induce apoptosis in breast cancer cells through reactive oxygen species and mitochondrial-dependent pathways
    Hematpoor A, Paydar M, Liew SY, Sivasothy Y, Mohebali N, Looi CY, et al.
    Chem Biol Interact, 2018 Jan 05;279:210-218.
    PMID: 29174417 DOI: 10.1016/j.cbi.2017.11.014
    The aim of the present study is to isolate bioactive compounds from the roots of Piper sarmentosum and examine the mechanism of action using human breast cancer cell line (MDA-MB-231). Bioassay guided-fractionation of methanolic extract led to the isolation of asaricin (1) and isoasarone (2). Asaricin (1) and isoasarone (2) had significant cytotoxicity towards MDA-MB-231. MCF-10A (human normal breast epithelial cells) cells are less sensitive than MDA-MB-231, but they respond to the treatment with the same unit of measurement. Both compounds increase reactive oxygen species (ROS), decrease mitochondrial membrane potential (MMP) and enhance cytochrome c release in treated MDA-MB-231 cells. Isoasarone (2) markedly elevated caspase -8 and -3/7 activities and caused a decline in nuclear NF-κB translocation, suggesting extrinsic, death receptor-linked apoptosis pathway. Quantitative PCR results of MDA-MB-231 treated with asaricin (1) and isoasarone (2) showed altered expression of Bcl-2: Bax level. The inhibitory potency of these isolates may support the therapeutic uses of these compounds in breast cancer.
    Matched MeSH terms: Mitochondria/drug effects*; Mitochondria/metabolism
  19. Wheat mitochondrial respiration shifts from the tricarboxylic acid cycle to the GABA shunt under salt stress
    Che-Othman MH, Jacoby RP, Millar AH, Taylor NL
    New Phytol, 2020 02;225(3):1166-1180.
    PMID: 30688365 DOI: 10.1111/nph.15713
    Mitochondrial respiration and tricarboxylic acid (TCA) cycle activity are required during salt stress in plants to provide ATP and reductants for adaptive processes such as ion exclusion, compatible solute synthesis and reactive oxygen species (ROS) detoxification. However, there is a poor mechanistic understanding of how salinity affects mitochondrial metabolism, particularly respiratory substrate source. To determine the mechanism of respiratory changes under salt stress in wheat leaves, we conducted an integrated analysis of metabolite content, respiratory rate and targeted protein abundance measurements. Also, we investigated the direct effect of salt on mitochondrial enzyme activities. Salt-treated wheat leaves exhibit higher respiration rate and extensive metabolite changes. The activity of the TCA cycle enzymes pyruvate dehydrogenase complex and the 2-oxoglutarate dehydrogenase complex were shown to be directly salt-sensitive. Multiple lines of evidence showed that the γ-aminobutyric acid (GABA) shunt was activated under salt treatment. During salt exposure, key metabolic enzymes required for the cyclic operation of the TCA cycle are physiochemically inhibited by salt. This inhibition is overcome by increased GABA shunt activity, which provides an alternative carbon source for mitochondria that bypasses salt-sensitive enzymes, to facilitate the increased respiration of wheat leaves.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/physiology*
  20. Cytotoxicity evaluation of ketoprofen found in pharmaceutical wastewater on HEK 293 cell growth and metabolism
    Zulkarnain NN, Anuar N, Johari NA, Sheikh Abdullah SR, Othman AR
    Environ Toxicol Pharmacol, 2020 Nov;80:103498.
    PMID: 32950717 DOI: 10.1016/j.etap.2020.103498
    Inefficient ketoprofen removal from pharmaceutical wastewater may negatively impact the ecosystem and cause detrimental risks to human health. This study was conducted to determine the cytotoxicity effects of ketoprofen on HEK 293 cell growth and metabolism, including cyclooxygenase-1 (COX-1) expression, at environmentally relevant concentrations. The cytotoxic effects were evaluated through the trypan blue test, DNS assay, MTT assay, and the expression ratio of the COX-1 gene. The results of this study show insignificant (p > 0.05) cytotoxic effects of ketoprofen on cell viability and cell metabolism. However, high glucose consumption rates among the treated cells cause an imitation of the Warburg effect, which is likely linked to the development of cancer cells. Apart from that, the upregulation of COX-1 expression among the treated cells indicates remote possibility of inflammation. Although no significant cytotoxic effects of ketoprofen were detected throughout this study, the effects of prolonged exposure of residual ketoprofen need to be evaluated in the future.
    Matched MeSH terms: Mitochondria/drug effects; Mitochondria/metabolism
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