Search Results (376)

Excessive stress disrupts cardiac homeostasis via complex and multifactorial mechanisms, resulting in cardiac dysfunction, cardiovascular disease, or even sudden cardiac death, yet the underlying molecular mechanisms remain poorly understood. Accordingly, we aimed to elucidate how stress induces calcium dysregulation and contributes to cardiac dysfunction and injury through the nuclear receptor subfamily 3 group c member 1 (NR3C1)/Glomulin (GLMN)/FK506-binding protein 12.6 (FKBP12.6) signaling pathway. Using mouse models of acute and chronic restraint stress, we observed that stress-exposed mice exhibited reduced left ventricular ejection fraction, ventricular wall thickening, elevated serum and myocardial cTnI levels, along with pathological features of myocardial ischemia and hypoxia, through morphological, functional, and hormonal assessments. Using transmission electron microscopy and Western blotting, we found that stress disrupted mitochondrial quality control in cardiomyocytes, evidenced by progressive mitochondrial swelling, cristae rupture, decreased expression of fusion proteins (MFN1/OPA1) and biogenesis regulator PGC-1α, along with aberrant accumulation of fission protein (FIS1) and autophagy marker LC3. At the cellular level, ChIP-qPCR and siRNA knockdown confirmed that stress activates the glucocorticoid receptor NR3C1 to repress its downstream target GLMN, thereby preventing FKBP12.6 ubiquitination and degradation, resulting in calcium leakage and overload, which ultimately impairs mitochondrial quality control and damages cardiomyocytes. In conclusion, our findings reveal that stress induces myocardial damage through NR3C1/GLMN-mediated FKBP12.6 ubiquitination, disrupting calcium homeostasis and mitochondrial quality control, and lay a theoretical foundation for dissecting the intricate molecular network of stress-induced cardiomyopathy. Full article

Background: Centella asiatica, a medicinally important species that is rich in bioactive compounds, lacks a characterized mitochondrial genome, despite nuclear and chloroplast assemblies. We sequenced and annotated its mitochondrial genome to elucidate its genetic foundations and evolutionary mechanisms. Methods: Assembly using Illumina short-reads and Nanopore long-reads was used to characterize the mitochondrial genome. Analyses included structural characterization, codon usage bias, repetitive sequences, horizontal gene transfer (HGT), collinearity, and phylogeny. The resulting tissue-specific (root, stem, and leaf) long non-coding RNA (lncRNA) profiles identified RNA editing sites. Results: The complete mitochondrial genome (249,777 bp, 45.5% GC) comprises three circular contigs encoding 51 genes (33 protein-coding, 15 tRNA, and 3 rRNA). Comparative genomics revealed synteny with the Apiaceae family of plants and evidence of HGT. Phylogenetic analysis resolved taxonomic relationships within Apiales. We predicted that 547 RNA editing sites would be identified in its protein-coding genes. Tissue profiling identified 725 (root), 711 (stem), and 668 (leaf) editing sites, with >71% concordance to predictions. RNA editing-generated cryptic promoters/terminators occur in mitochondrial core function genes (e.g., ATP synthase, cytochrome c reductase/oxidase, ribosome large subunit, and cytochrome c biogenesis), exhibiting a lower frequency in the leaves compared to the roots and stems. Conclusions: We provide the first complete mitochondrial genome assembly for C. asiatica, delineating its complex structure, tissue-modulated RNA editing, and evolutionary trajectory. This high-quality genomic resource establishes a foundation for molecular evolutionary studies and enhances the genomic toolkit for this pharmacologically significant species. Full article

Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article

Paeonia ludlowii, a critically endangered species endemic to Tibet, China, possesses significant ornamental, culinary, and medicinal value. However, its mitochondrial genome remains understudied, limiting insights into its evolutionary mechanisms and constraining conservation genetics applications and molecular breeding programs. We present the first complete assembly and comprehensive analysis of the P. ludlowii mitochondrial genome. Most remarkably, we discovered that the P. ludlowii mitogenome exhibits an atypical dual-circular structure, representing the first documented occurrence of this architectural feature within the genus Paeonia. The assembled genome spans 314,371 bp and encodes 42 tRNA genes, 3 rRNA genes, and 31 protein-coding genes, with a pronounced adenine–thymine bias. This multipartite genome structure is characterized by abundant repetitive elements (112 functionally annotated SSRs, 33 tandem repeats, and 945 dispersed repeats), which potentially drive genome rearrangements and facilitate adaptive evolution. Analyses of codon usage bias and nucleotide diversity revealed highly conserved gene expression regulation with limited variability. Phylogenetic reconstruction confirms that P. ludlowii, P. suffruticosa, and P. lactiflora form a monophyletic clade, reflecting close evolutionary relationships, while extensive syntenic collinearity with other Paeonia species underscores mitochondrial genome conservation at the genus level. Extensive inter-organellar gene transfer events, particularly from chloroplast to mitochondrion, suggest that such DNA exchanges enhance genetic diversity and promote environmental adaptation. The discovery of the dual-circular architecture provides novel insights into plant mitochondrial genome evolution and structural plasticity. This study elucidates the unique structural characteristics of the P. ludlowii mitochondrial genome and establishes a crucial genetic foundation for developing targeted conservation strategies and facilitating molecular-assisted breeding programs for this endangered species. Full article

Toxoplasma gondii is an Apicomplexan parasite that possesses a well-developed system of scavengers of reactive oxygen species (ROS). Among its components, T. gondii mitochondrial superoxide dismutase (TgSOD2) is essential, as predicted by the CRISPR phenotype index and evidenced by the non-viability of its constitutive knockouts. As an obligate intracellular parasite, TgSOD2 is upregulated during extracellular stages. Herein, we generated a viable TgSOD2 knockdown mutant using an inducible auxin–degron system to explore the biological role of TgSOD2 in T. gondii. Depletion of TgSOD2 led to impaired parasite growth and replication, reduced mitochondrial membrane potential (MMP), abnormalities in the distribution of ATP synthase within its mitochondrial electron transport chain (mETC), and increased susceptibility to mETC inhibitors. Through a proximal biotinylation approach, we identified the interactions of TgSOD2 with complexes IV and V of its mETC, suggesting that these sites are sensitive to ROS. Our study provides the first insights into the role of TgSOD2 in maintaining its mitochondrial redox homeostasis and subsequent parasite replication fitness. Significance: Toxoplasma gondii infects nearly a third of the world population and can cause fetal miscarriages or life-threatening complications in vulnerable patients. Current therapies do not eradicate the parasite from the human hosts, rendering them at risk of recurrence during their lifetimes. T. gondii has a single mitochondrion, which is well-known for its susceptibility to oxidative damage that leads to T. gondii’s death. Therefore, targeting T. gondii mitochondrion remains an attractive therapeutic strategy for drug development. T. gondii’s mitochondrial superoxide dismutase is an antioxidant protein in the parasite mitochondrion and is essential for its survival. Understanding its biological role could reveal mitochondrial vulnerabilities in T. gondii and provide new leads for the development of effective treatments for T. gondii infections. Full article

Background/Objectives: Neurodegenerative disorders have a complex multifactorial pathogenesis that develop decades before the initial symptoms occur. One of the crucial factors in the development of neurodegenerative disorders is an unbalanced diet. A pediatric animal model of diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) was established by feeding juvenile Iberian pigs a diet high in fat and fructose for 10 weeks. The aim of this study was to investigate the initial molecular imbalances in the frontal cortex (FC) of diet-induced juvenile MASLD pig model and determine whether these changes are associated with neuronal loss. Methods: Eighteen 15-day-old Iberian pigs were randomly assigned to either a standard diet (SD) or a Western diet (WD) for 10 weeks. A short-term recognition memory test and animal activity was recorded during the study. Animals were euthanized in week 10, and the FC and hippocampus (HIP) tissue samples were collected for immunohistochemistry and transcriptomics analyses. Results: WD-fed pigs developed MASLD. There were no significant differences in animals’ activity or recognition memory between WD and SD. To identify and quantify mature neurons, NeuN immunostaining intensity was measured, which was significantly lower in the FC of WD than SD (p ≤ 0.05), but it did not change in HIP (p ≥ 0.05). The Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, was downregulated in FC of WD-fed pigs (p ≤ 0.05). Similarly, cytoskeleton organization and extracellular matrix biological processes were downregulated in FC of WD-fed pigs (p ≤ 0.05), whereas the mitochondrial respiratory chain complex and mitochondrion increased in FC of WD compared with SD (p ≤ 0.01). There were several other significantly modulated pathways including signal transduction, cell migration, axon guidance, and calcium ion binding. Conclusions: The high-fructose, high-fat diet led to neuronal loss in the frontal cortex of MASLD pigs and dysregulated gene expression of the Wnt/β-catenin signaling pathway, cytoskeleton organization, extracellular matrix, and mitochondrial respiratory chain—all pathways that are found deregulated in neurodegnerative diseases. Full article

Symbiotic interactions between legumes and a group of soil bacteria, known as rhizobia, lead to the formation of a specialized organs called root nodules. Inside them, atmospheric nitrogen (N₂) is fixed by bacteria and reduced to forms available to plants, catalyzed by the nitrogenase enzyme complex. The development of a symbiotic relationship between legumes and nodule bacteria is a multi-stage, precisely regulated process, characterized by a high specificity of partner selection. Nodulation involves the enhanced expression of certain plant genes, referred to as early- and late-nodulin genes. Many nodulin genes encode hydroxyproline-rich glycoproteins (HRGPs) and proline-rich proteins (PRPs) which are involved in various processes, including infection thread formation, cell signaling, and defense responses, thereby affecting nodule formation and function. Cyclophilins (CyPs) belong to a family of proteins with peptidyl-prolyl cis–trans isomerase activity. Proteins with cyclophilin domain can be found in the cytoplasm, endoplasmic reticulum, nucleus, chloroplast, and mitochondrion. They are involved in various processes, such as protein folding, cellular signaling, mRNA maturation, and response to biotic and abiotic stress. In this review, we aim to summarize the molecular processes involved in the development of symbiosis and highlight the potential role of cyclophilins (peptidyl-prolyl cis-trans isomerases) in this process. Full article

Cuscutae Semen (CS), a traditional herb recognized as a nutraceutical food in China, has been widely utilized in managing aging-related diseases throughout history. However, whether this mechanism is associated with mitochondrial stress tolerance remains unclear. In the present study, Caenorhabditis elegans (C. elegans) was used to investigate the effects of CS on their longevity. The data demonstrated that CS prolonged the average lifespan of the nematodes by 15.26%, reducing lipofuscin accumulation by 61.46%, as well as improving spontaneous motility. CS treatment significantly enhanced the resistance of C. elegans to hydrogen peroxide-induced oxidative stress and 37 °C induced heat stress, reducing reactive oxygen species (ROS) production by 71.45%. Additionally, membrane potential (MMP) and adenosine triphosphate (ATP) were increased by 354.72% and 69.64%, respectively. However, mitochondrion-specific ROS and calcium flux were significantly reduced to 45.86% and 63.25%, respectively, in C. elegans treated with CS. Consistently, the polymerase chain reaction data revealed that CS significantly up-regulated the expressions of the antioxidant-related genes skn-1, ctl-1, sod-3, and gst-4; the heat shock gene hsp-16.2; and the autophagy-related genes lgg-1 and bec-1. Considering the crucial role of the silent information regulator sirtuin 1 (SIR-2.1/SIRT1) in aging-related mitochondrial oxidative stress, we examined its expression and transcriptional activity. As expected, treatment with CS induced SIRT1 expression, and isorhamnetin identified from CS extract significantly enhanced SIRT1 transcriptional activity in HEK293T cells. Collectively, our results provided evidence that CS prolonged the lifespan of C. elegans by ameliorating oxidative stress damage and mitochondrial dysfunction via SIRT1. Full article

As high-quality sheep germplasm resources in China, Hu sheep are characterized by fast growth and development, high fecundity, and tolerance to drought and cold. Tibetan sheep, adapted to high-altitude environments, have developed strong environmental adaptability. To explore the differences in the interaction among rumen microbial flora, hepatic gluconeogenesis, and mitochondrial function between Tibetan sheep and Hu sheep in the Qinghai–Tibet Plateau, this study systematically compared and analyzed the rumen flora density, key enzyme activities related to hepatic gluconeogenesis and mitochondrial function, and the expression levels of related genes in Tibetan sheep and Hu sheep under identical feeding management conditions, followed by correlation analysis. The results showed that Hu sheep had significantly higher densities of Ruminobacteramylophilus (Ram) and Fibrobacter succinogenes (Fs) associated with starch and protein degradation (p < 0.01). The expression levels of Forkhead box O1 (FOXO1), pyruvate carboxylase (PC) activity, and adenosine triphosphate (ATP) content were also significantly higher than those in Tibetan sheep (p < 0.01). In contrast, Tibetan sheep had higher densities of Butyrivibrio fibrisolvens (Bf), Ruminococcus albus (Ra), Ruminococcus flavefaciens (Rf), etc., related to cellulose degradation (p < 0.01). The gluconeogenesis-related genes, Glucose-6-phosphatase catalytic subunit 1 (G6PC1) and phosphoenolpyruvate carboxykinase1 (PCK1), and the activities of phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBPase) were significantly higher in Tibetan sheep than in Hu sheep (p < 0.01). Mitochondrial function-related genes Mitofusin-1 (Mfn1), Mitofusin-2 (Mfn2), subunit 6 of ATP synthase (ATP6), cytochrome b (Cytb), etc., also showed significantly higher expression in Tibetan sheep (p < 0.01). While no significant differences were observed in the contents of citric acid (CA), pyruvic acid (PA), glucose (Glu), etc. (p > 0.05). Correlation analysis indicated that rumen flora was associated with the key enzyme activities and gene expressions of hepatic gluconeogenesis and mitochondrial function to varying degrees. In summary, Tibetan sheep exhibit strong fiber degradation capacity, the efficient utilization of gluconeogenic intermediates, and mitochondrial oxidative phosphorylation (OXPHOS) ability, forming adaptive strategies for high-altitude environments. By contrast, Hu sheep show efficient protein and starch degradation capacity, thereby enhancing the supply of gluconeogenic precursors. It is indicated that when introducing Hu sheep to high-altitude areas, dietary intervention can be used to regulate rumen microorganisms, such as increasing fiber-decomposing bacteria or enhancing mitochondrial oxidative capacity, to counteract metabolic limitations induced by hypoxia. Full article

Coccidian parasites possess complex life cycles involving asexual proliferation followed by sexual development, producing oocysts that are transmitted from host to host through feces, guaranteeing disease transmission. Eimeria necatrix is a highly pathogenic coccidian causing high mortality in birds. This study examined ultrastructural changes occurring during the third merogony, microgametogenesis, and macrogametogenesis of E. necatrix. The third-generation meront contained eight merozoites, each with coccidian-specific features like conoid, rhoptries, micronemes, and dense granules. Microgametes had a nucleus, mitochondrion, two flagella, and a basal apparatus. Macrogametes surrounded by two membranes (M1 and M2), contained organelles like WFB1, WFB2, endoplasmic reticulum, mitochondria, and tubular structures. Oocyst wall formation began with M2 separating from M1 and forming a loose veil around the organism. The WFB1 fused together to form the outer layer of the oocyst wall between M1 and M2, while M4 formed beneath M1. The WFB2 fused with the M4 to discharge its contents external to M4, which fused together to form the inner layer of the oocyst wall. Immunogold electron microscopy co-localization result showed that EnGAM22 localized to WFB1 and the outer wall, while EnGAM59 localized to WFB2 and the inner wall, suggesting they are key structural components of the oocyst wall. Full article

Pampus argenteus, a commercially significant marine species, faces genetic diversity challenges in selective breeding programs. This study implemented a comprehensive molecular strategy to evaluate genetic parameters in wild populations along China’s coast and three successive selected generations. The analysis utilized 19 highly polymorphic microsatellite loci, mtCOI, and mtD-loop sequences to assess genetic structure. Compared with the wild populations, the average number of alleles (N_a: 11.158–12.947), effective alleles (N_e: 5.592–6.502), observed heterozygosity (H_o: 0.626–0.665), expected heterozygosity (H_e: 0.777–0.796), and allele richness (A_r: 10.900–12.510) of the selected populations did not significantly decrease. In the mass selection of the three consecutive generations, the high genetic diversity of the selected population was successfully maintained. The effective population sizes of the first to third generations were estimated to be 83.7, 66.6, and 59.6, respectively. Population differentiation analysis showed minimal genetic divergence (FST = 0.0159–0.0326) with substantial gene flow, supported by clustering patterns indicating panmixia among wild populations from different geographical locations and among the selected populations. Notably, marginal decreases in diversity indices across generations suggest incipient genetic diversity decline, underscoring the imperative for systematic genetic monitoring. These findings validate the current breeding program’s efficacy in maintaining genetic variability while providing a framework for optimizing long-term selection strategies to prevent inbreeding depression. Full article

Metabolic-dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant public health concern, attributed to its increasing prevalence and correlation with metabolic disorders, including obesity and type 2 diabetes. Recent research has highlighted that mitochondrial dysfunction can result in the accumulation of lipids in non-adipose tissues, as well as increased oxidative stress and inflammation. These factors are crucial in advancing the progression of MASLD. Despite advances in the understanding of MASLD pathophysiology, challenges remain in identifying effective therapeutic strategies targeting mitochondrial dysfunction. This review aims to consolidate current knowledge on how mitochondrial imbalance affects the development and progression of MASLD, while addressing existing research gaps and potential avenues for future research. This review was conducted after a systematic search of comprehensive academic databases such as PubMed, Embase, and Web of Science to gather information on mitochondrial dysfunction as well as mitochondrial-based treatments for MASLD. Full article

Background/Objectives: This review has been prepared to promote interest in the interdisciplinary study of mitochondrial dysfunction (MD) and atherosclerosis. This review aims to describe the state of this problem and indicate the direction for further implementation of this knowledge in clinical medicine. Methods: Extensive research of the literature was implemented to elucidate the role of the molecular mechanisms of MD in the pathogenesis of atherosclerosis. Results: A view on the pathogenesis of atherosclerosis through the prism of knowledge about MD is presented. MD is the cause and primary mechanism of the onset and progression of atherosclerosis. It is proposed that this problem be considered in the context of a continuum. Conclusions: MD and atherosclerosis are united by common molecular mechanisms of pathogenesis. Knowledge of MD should be used to argue for a healthy lifestyle as the primary way to prevent atherosclerosis. The development of new approaches to diagnosing and treating MD in atherosclerosis is an urgent task and challenge for modern science. Full article

Banana (Musa spp.) is susceptible to low-temperature stress and other environmental stresses, which can hinder the growth and development. Succinic semialdehyde dehydrogenase (SSADH) is critical for GABA biosynthesis and plays a crucial role in plants. However, the SSADH genes of bananas have not been studied. This study found 19 MaSSADHs, 18 MbSSADHs, and 18 MiSSADHs from the banana genome. According to the phylogenetic tree, these genes can be categorized into five branches. This study cloned the MaSSADH1-14 from banana. The subcellular localization assays of MaSSADH1-14 in tobacco leaves confirmed that the presence of SSADH was not only localized mitochondrion but also localized chloroplast. The cis-elements of the SSADH gene family are related to the potential regulation of the banana SSADH gene family; their involvement in diverse stress responses. Transcriptomic data was utilized to examine the effect of MaSSADH genes under cold stress in bananas. The results of RT-qPCR were consistent with transcriptome data. These results showed that most MaSSADHs are passively responsive to low-temperature treatment. In addition, transient overexpression of MaSSADH1-14 in Nicotiana benthamiana leaves resulted in the content of GABA increasing, indicating that MaSSADH1-14 may be involved in the accumulation of GABA of banana. Collectively, these results improve knowledge of the SSADH gene family in banana and establish a basis for comprehending its biological roles in response to low temperatures. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence is expected to double in the next 30 years. Currently, no effective treatment exists for Parkinson’s disease. Thus, the research has focused on discovering new natural compounds with strong neuroprotective potential. This study aimed to investigate the effects of the methanol extract of Desmodesmus arthrodesmiformis EM13 (DaMe) on the mitochondrial damage pathway in an in vitro model of PD. The isolate of Desmodesmus arthrodesmiformis EM13 was first grown under appropriate culture conditions, and then the extract (DaMe) was prepared for use in the experiments. The total lipid and protein contents, fatty acid composition, and elemental content of DaMe were subsequently determined. Human SH-SY5Y neuroblastoma cells were pretreated with nontoxic concentrations of DaMe before 6-hydroxydopamine (6-OHDA) toxicity. Pretreatment with DaMe at concentrations of 100, 250, and 500 µg/mL showed a neuroprotective effect on 6-OHDA-induced SH-SY5Y neuroblastoma cells by decreasing the reactive oxygen species (ROS) production, decreasing the total oxidant status (TOS), increasing the total antioxidant capacity (TAC), increasing the mitochondrial membrane potential (ΔΨm), decreasing the oxidative DNA damage, and regulating gene expressions related to PD and apoptosis. Given the results of our study, we suggest that DaMe can be used as a natural source for producing drugs and dietary supplements intended to treat PD. Full article