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Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Endometriosis (EMT), a common benign gynecological disease, is a leading cause of infertility in women. EMT affects female fertility in various aspects. However, the...
Endometriosis (EMT), a common benign gynecological disease, is a leading cause of infertility in women. EMT affects female fertility in various aspects. However, the underlying mechanisms have not been fully elucidated. Mitochondria are known as the "powerhouse" of a cell. They play pivotal roles in the physiological processes of cellular energy metabolism, calcium homeostasis, oxidative stress, autophagy, the regulation of cell cycle, and cell death, and are involved in the pathophysiology of many diseases. Cellular mitochondria are highly dynamic, continuously undergoing cyclic fission and fusion to meet the demands of cellular activities. Balanced mitochondrial dynamics are critical for maintaining normal reproductive function in women. In addition, mitochondria are the major source of reactive oxygen species (ROS). Cell damage, cell death, and fibrosis mediated by the imbalance in the oxidative-antioxidant system in EMT patients lead to decreased oocyte quality and ovarian reserve. Currently, the treatment of EMT-associated infertility remains a challenging and controversial topic. We herein reviewed the latest findings on the role of mitochondrial dysfunction in EMT-associated infertility and the potential therapeutic targets.
PubMed: 38948278
DOI: 10.12182/20240560404 -
PeerJ 2024Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible...
Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible damage to the myocardium. The number of mitochondria in cardiomyocytes is large, which generate adenosine triphosphate (ATP) to sustain proper cardiac contractile function, and mitochondrial dysfunction plays a crucial role in cell death during myocardial ischemia-reperfusion, leading to an increasing number of studies investigating the impact of mitochondria on ischemia-reperfusion injury. The disarray of mitochondrial dynamics, excessive Ca accumulation, activation of mitochondrial permeable transition pores, swelling of mitochondria, ultimately the death of cardiomyocyte are the consequences of ischemia-reperfusion injury. -opioid receptors can alleviate mitochondrial dysfunction, regulate mitochondrial dynamics, mitigate myocardial ischemia-reperfusion injury, exert protective effects on myocardium. The mechanism of -OR activation during myocardial ischemia-reperfusion to regulate mitochondrial dynamics and reduce myocardial ischemia-reperfusion injury will be discussed, so as to provide theoretical basis for the protection of ischemic myocardium.
PubMed: 38948204
DOI: 10.7717/peerj.17333 -
ACS Central Science Jun 2024Mitochondria are essential organelles involved in various metabolic processes in eukaryotes. The imaging, targeting, and investigation of cell death mechanisms related...
Mitochondria are essential organelles involved in various metabolic processes in eukaryotes. The imaging, targeting, and investigation of cell death mechanisms related to mitochondria have garnered significant interest. Small-molecule fluorescent probes have proven to be robust tools for utilizing light to advance the study of mitochondrial biology. In this study, we present the rational design of cationic Nile blue probes carrying a permanent positive charge for these purposes. The cationic Nile blue probes exhibit excellent mitochondrial permeability, unique solvatochromism, and resistance to oxidation. We observed weaker fluorescence in aqueous solutions compared to lipophilic solvents, thereby minimizing background fluorescence in the cytoplasm. Additionally, we achieved photoredox switching of the cationic Nile blue probes under mild conditions. This enabled us to demonstrate their application for the first time in single-molecule localization microscopy of mitochondria, allowing us to observe mitochondrial fission and fusion behaviors. Compared to conventional cyanine fluorophores, this class of dyes demonstrated prolonged resistance to photobleaching, likely due to their antioxidation properties. Furthermore, we extended the application of cationic Nile blue probes to the mitochondria-specific delivery of taxanes, facilitating the study of direct interactions between the drug and organelles. Our approach to triggering cell death without reliance on microtubule binding provides valuable insights into anticancer drug research and drug-resistance mechanisms.
PubMed: 38947205
DOI: 10.1021/acscentsci.4c00073 -
Molecular Ecology Jul 2024We present palaeogenomes of three morphologically unidentified Anatolian equids dating to the first millennium BCE, sequenced to a coverage of 0.6-6.4×. Mitochondrial...
We present palaeogenomes of three morphologically unidentified Anatolian equids dating to the first millennium BCE, sequenced to a coverage of 0.6-6.4×. Mitochondrial DNA haplotypes of the Anatolian individuals clustered with those of Equus hydruntinus (or Equus hemionus hydruntinus), the extinct European wild ass, secular name 'hydruntine'. Further, the Anatolian wild ass whole genome profiles fell outside the genomic diversity of other extant and past Asiatic wild ass (E. hemionus) lineages. These observations suggest that the three Anatolian wild asses represent hydruntines, making them the latest recorded survivors of this lineage, about a millennium later than the latest observations in the zooarchaeological record. Our mitogenomic and genomic analyses indicate that E. h. hydruntinus was a clade belonging to ancient and present-day E. hemionus lineages that radiated possibly between 0.6 and 0.8 Mya. We also find evidence consistent with recent gene flow between hydruntines and Middle Eastern wild asses. Analyses of genome-wide heterozygosity and runs of homozygosity suggest that the Anatolian wild ass population may have lost genetic diversity by the mid-first millennium BCE, a possible sign of its eventual demise.
PubMed: 38946459
DOI: 10.1111/mec.17440 -
Journal of Microbiological Methods Jun 2024The ability to acquire three-dimensional (3D) information of cellular structures without the need for fluorescent tags or staining makes holotomographic imaging a...
The ability to acquire three-dimensional (3D) information of cellular structures without the need for fluorescent tags or staining makes holotomographic imaging a powerful tool in cellular biology. It provides valuable insights by measuring the refractive index (RI), an optical parameter describing the phase delay of light that passes through the living cell. Here, we demonstrate holotomographic imaging on industrial relevant ascomycete fungi and study their development and morphogenesis. This includes conidial germination, subcellular dynamics, and cytoplasmic flow during hyphal growth in Aspergillus niger. In addition, growth and budding of Aureobasidium pullulans cells are captured using holotomographic microscopy. Coupled to fluorescence imaging, lipid droplets, vacuoles, the mitochondrial network, and nuclei are targeted and analyzed in the 3D RI reconstructed images. While lipid droplets and vacuoles can be assigned to a specific RI pattern, mitochondria and nuclei were not pronounced. We show, that the lower sensitivity of RI measurements derives from the fungal cell wall that acts as an additional barrier for the illumination light of the microscope. After cell wall digest of hyphae and protoplast formation of A. niger expressing GFP-tagged histone H2A, location of nuclei could be determined by non-invasive RI measurements. Furthermore, we used coupled fluorescence microscopy to observe migration of nuclei in unperturbed hyphal segments and duplication during growth on a single-cell level. Detailed micromorphological studies in Saccharomyces cerevisiae and Trichoderma reesei are challenging due to cell size restrictions. Overall, holotomography opens up new avenues for exploring dynamic cellular processes in real time and enables the visualization of fungi from a new perspective.
PubMed: 38945304
DOI: 10.1016/j.mimet.2024.106983 -
The FEBS Journal Jun 2024Iron overload (IO) is known to contribute to metabolic dysfunctions such as type 2 diabetes and insulin resistance. Using L6 skeletal muscle cells overexpressing the...
Iron overload (IO) is known to contribute to metabolic dysfunctions such as type 2 diabetes and insulin resistance. Using L6 skeletal muscle cells overexpressing the CDGSH iron-sulfur domain-containing protein 1 (CISD1, also known as mitoNEET) (mitoN) protein, we examined the potential role of MitoN in preventing IO-induced insulin resistance. In L6 control cells, IO resulted in insulin resistance which could be prevented by MitoN as demonstrated by western blot of p-Akt and Akt biosensor cells. Mechanistically, IO increased; mitochondrial iron accumulation, mitochondrial reactive oxygen species (ROS), Fis1-dependent mitochondrial fission, mitophagy, FUN14 domain-containing protein 1 (FUNDC1) expression, and decreased Parkin. MitoN overexpression was able to reduce increases in mitochondrial iron accumulation, mitochondrial ROS, mitochondrial fission, mitophagy and FUNDC1 upregulation due to IO. MitoN did not have any effect on the IO-induced downregulation of Parkin. MitoN alone also upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein levels, a master regulator of mitochondrial biogenesis. The use of mitochondrial antioxidant, Skq1, or fission inhibitor, Mdivi-1, prevented IO-induced insulin resistance implying both mitochondrial ROS and fission play a causal role in the development of insulin resistance. Taken together, MitoN is able to confer protection against IO-induced insulin resistance in L6 skeletal muscle cells through regulation of mitochondrial iron content, mitochondrial ROS, and mitochondrial fission.
PubMed: 38944692
DOI: 10.1111/febs.17214 -
Biochemical Pharmacology Jun 2024Gestational diabetes mellitus (GDM) is associated with cardiovascular disease in postnatal life. The current study tested the hypothesis that GDM caused the cardiac...
Up-regulation of BRD4 contributes to gestational diabetes mellitus-induced cardiac hypertrophy in offspring by promoting mitochondria dysfunction in sex-independent manner.
Gestational diabetes mellitus (GDM) is associated with cardiovascular disease in postnatal life. The current study tested the hypothesis that GDM caused the cardiac hypertrophy in fetal (ED18.5), postnatal day 7 (PD7), postnatal day 21 (PD21) and postnatal day 90 (PD90) offspring by upregulation of BRD4 and mitochondrial dysfunction. Pregnant mice were divided into control and GDM groups. Hearts were isolated from ED18.5, PD7, PD21 and PD90. GDM increased the body weight (BW) and heart weight (HW) in ED18.5 and PD7, but not PD21 and PD90 offspring. However, HW/BW ratio was increased in all ages of GDM offspring compared to control group. Electron microscopy showed disorganized myofibrils, mitochondrial swelling, vacuolization, and cristae disorder in GDM offspring. GDM resulted in myocardial hypertrophy in offspring, which persisted from fetus to adult in a sex-independent manner. Echocardiography analysis revealed that GDM caused diastolic dysfunction, but had no effect on systolic function. Meanwhile, myocardial BRD4 was significantly upregulated in GDM offspring and BRD4 inhibition by JQ1 alleviated GDM-induced myocardial hypertrophy in offspring. Co-immunoprecipitation showed that BRD4 interacted with DRP1 and there was an increase of BRD4 and DRP1 interaction in GDM offspring. Furthermore, GDM caused the accumulation of damaged mitochondria in hearts from all ages of offspring, including mitochondrial fusion fission imbalance (upregulation of DRP1, and downregulation of MFN1, MFN2 and OPA1) and myocardial mitochondrial ROS accumulation, which was reversed by JQ1. These results suggested that the upregulation of BRD4 is involved in GDM-induced myocardial hypertrophy in the offspring through promoting mitochondrial damage in a gender-independent manner.
PubMed: 38944397
DOI: 10.1016/j.bcp.2024.116387 -
Gene Jun 2024The domestication of animals marks a pivotal moment in human history, profoundly influencing our demographic and cultural progress. This process has led to significant... (Review)
Review
The domestication of animals marks a pivotal moment in human history, profoundly influencing our demographic and cultural progress. This process has led to significant genetic, behavioral, and physical changes in livestock species compared to their wild ancestors. Understanding the evolutionary history and genetic diversity of livestock species is crucial, and mitochondrial DNA (mtDNA) has emerged as a robust marker for investigating molecular diversity in animals. Its highly conserved gene content across animal species, minimal duplications, absence of introns, and short intergenic regions make mtDNA analysis ideal for such studies. Mitochondrial DNA analysis has uncovered distinct cattle domestication events dating back to 8000years BC in Southwestern Asia. The sequencing of water buffalo mtDNA in 2004 provided important insights into their domestication history. Caprine mtDNA analysis identified three haplogroups, indicating varied maternal origins. Sheep, domesticated 12,000 years ago, exhibit diverse mtDNA lineages, suggesting multiple domestication events. Ovine mtDNA studies revealed clades A, B, C, and a fourth lineage, group D. The origins of domestic pigs were traced to separate European and Asian events followed by interbreeding. In camels, mtDNA elucidated the phylogeographic structure and genetic differentiation between wild and domesticated species. Horses, domesticated around 3500 BC, show significant mtDNA variability, highlighting their diverse origins. Yaks exhibit unique adaptations for high-altitude environments, with mtDNA analysis providing insights into their adaptation. Chicken mtDNA studies supported a monophyletic origin from Southeast Asia's red jungle fowl, with evidence of multiple origins. This review explores livestock evolution and diversity through mtDNA studies, focusing on cattle, water buffalo, goat, sheep, pig, camel, horse, yak and chicken. It highlights mtDNA's significance in unraveling maternal lineages, genetic diversity, and domestication histories, concluding with insights into its potential application in improving livestock production and reproduction dynamics.
PubMed: 38944163
DOI: 10.1016/j.gene.2024.148728 -
Movement Disorders Clinical Practice Jun 2024Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in... (Review)
Review
BACKGROUND
Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). These disorders are multisystemic and mainly affect high energy-demanding tissues, such as muscle and the central nervous system (CNS). Among many clinical features of CNS involvement, parkinsonism is one of the most common movement disorders in PMDs.
METHODS
This review provides a pragmatic educational overview of the most recent advances in the field of mitochondrial parkinsonism, from pathophysiology and genetic etiologies to phenotype and diagnosis.
RESULTS
mtDNA maintenance and mitochondrial dynamics alterations represent the principal mechanisms underlying mitochondrial parkinsonism. It can be present in isolation, alongside other movement disorders or, more commonly, as part of a multisystemic phenotype. Mutations in several nuclear-encoded genes (ie, POLG, TWNK, SPG7, and OPA1) and, more rarely, mtDNA mutations, are responsible for mitochondrial parkinsonism. Progressive external opthalmoplegia and optic atrophy may guide genetic etiology identification.
CONCLUSION
A comprehensive deep-phenotyping approach is needed to reach a diagnosis of mitochondrial parkinsonism, which lacks distinctive clinical features and exemplifies the intricate genotype-phenotype interplay of PMDs.
PubMed: 38943319
DOI: 10.1002/mdc3.14148 -
Cell Death & Disease Jun 2024S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory...
S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory diseases. Although S100a8/a9 has been reported to trigger endothelial cell apoptosis, the mechanisms of S100a8/a9-induced endothelial dysfunction during sepsis require in-depth research. We demonstrate that high expression levels of S100a8/a9 suppress Ndufa3 expression in mitochondrial complex I via downregulation of Nrf1 expression. Mitochondrial complex I deficiency contributes to NAD-dependent Sirt1 suppression, which induces mitochondrial disorders, including excessive fission and blocked mitophagy, and mtDNA released from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis in endothelial cells. Moreover, based on comprehensive scRNA-seq and bulk RNA-seq analyses, S100A8/A9 neutrophils are closely associated with the circulating endothelial cell count (a useful marker of endothelial damage), and S100A8 is an independent risk factor for poor prognosis in sepsis patients.
Topics: Calgranulin A; Neutrophils; Sepsis; Humans; Calgranulin B; Mitochondria; Electron Transport Complex I; Endothelial Cells; Animals; Mice; Male; Human Umbilical Vein Endothelial Cells; Mitophagy; Mice, Inbred C57BL; Apoptosis
PubMed: 38942784
DOI: 10.1038/s41419-024-06849-6