Mitochondria DNA

The use of bisphenol A (BPA) has been restricted due to its endocrine-disrupting effects. As a widely used alternative to BPA today, environmental levels of bisphenol Z (BPZ) continue to rise and accumulate in humans. Oocyte quality is critical for a successful pregnancy. Nevertheless, the toxic impacts of BPZ on the maturation of mammalian oocytes remain unexplored. Therefore, the impacts of BPZ and BPA on oocyte meiotic maturation were compared in an in vitro mouse oocyte culture model. Exposure to 150 μM of both BPZ and BPA disrupted the assembly of the meiotic spindle and the alignment of chromosomes, and BPZ exerted stronger toxicological effects than BPA...

DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized Schizosaccharomyces pombe Mss116 (spMss116), a member of the family of DEAD-box RNA helicases. Deletion of spmss116 in a mitochondrial intron-containing background significantly reduced the levels of mitochondrial DNA (mtDNA)-encoded cox1 and cob1 mRNAs and impaired mitochondrial translation, leading to a severe respiratory defect and a loss of cell viability during stationary phase...

Photodynamic therapy (PDT) provides an alternative approach to targeted cancer treatment, but the therapeutic mechanism of advanced nanodrugs applied to live cells and tissue is still not well understood. Herein, we employ the hybrid hyperspectral stimulated Raman scattering (SRS) and transient absorption (TA) microscopy developed for real-time in vivo visualization of the dynamic interplay between the unique photoswichable lanthanide-doped upconversion nanoparticle-conjugated rose bengal and triphenylphosphonium (LD-UCNP@CS-Rb-TPP) probe synthesized and live cancer cells...

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis , is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2 O2 ) in murine C2C12 myoblasts...

Parent-child relationship dynamics have been shown to predict socioemotional and behavioral outcomes for children, but little is known about how they may affect biological development. The aim of this study was to test if observational assessments of parent-child relationship dynamics (cohesion, enmeshment, and disengagement) were associated with three biological indices of early life adversity and downstream health risk: (1) methylation of the glucocorticoid receptor gene ( NR3C1 ), (2) telomere attrition, and (3) mitochondrial biogenesis, indexed by mitochondrial DNA copy number (mtDNAcn), all of which were measured in children's saliva...

OBJECTIVES: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms...

Cisplatin remains the most widely used chemotherapeutic agent in cancer treatment; however, its inherent drawbacks have fueled the development of novel metalloanticancer drugs. In this study, two novel Cu(II) complexes (Cu1 and Cu2) were designed and synthesized. Notably, these Cu(II) complexes showed higher cytotoxicity against HL-7402 cells than cisplatin. Moreover, Cu(II) complexes significantly inhibited liver cancer growth in a xenograft model. A mechanism study revealed that the Cu(II) complexes reduced the mitochondrial membrane potential of cancer cells, produced excessive reactive oxygen species (ROS), induced mitochondrial DNA (mtDNA) damage, and ultimately facilitated cancer cell apoptosis...

Chromosomal translocation (4;14), an adverse prognostic factor in multiple myeloma (MM), drives overexpression of the histone methyltransferase NSD2. A genome-wide CRISPR screen in MM cells identified adenylate kinase 2 (AK2), an enzyme critical for high energy phosphate transfer from the mitochondria, as an NSD2-driven vulnerability. AK2 suppression in t(4;14) MM cells decreased NADP(H) critical for conversion of ribonucleotides to deoxyribonucleosides, leading to replication stress, DNA damage and apoptosis...

Oocytes of both vertebrates and invertebrates often contain an intricate organelle assemblage, termed the Balbiani body (Bb). It has previously been suggested that this assemblage is involved in the delivery of organelles and macromolecules to the germ plasm, formation of oocyte reserve materials, and transfer of mitochondria to the next generation. To gain further insight into the function of the Bb, we performed a series of analyses and experiments, including computer-aided 3-dimensional reconstructions, detection of DNA (mtDNA) synthesis as well as immunolocalization studies...

Pyroptosis is closely related to the development and treatment of various cancers; thus, comprehensive studies of the correlations between pyroptosis and its inductive or inhibitive factors can provide new ideas for the intervention and diagnosis of tumors. The dysfunction of mitochondria may induce pyroptosis in cancer cells, which can be reflected by the fluctuations of the microenvironmental parameters in mitochondria as well as the changes of mitochondrial DNA level and morphology, etc. To precisely track and assess the mitochondria-associated pyroptosis process, simultaneous visualization of changes in multiphysiological parameters in mitochondria is highly desirable...

In the last years, plant organelles have emerged as central coordinators of responses to internal and external stimuli which can induce stress. Mitochondria play a fundamental role as stress sensors being part of a complex communication network between the organelles and nucleus. Among the different environmental stresses, salt stress poses a significant challenge and requires efficient signaling and protective mechanisms. By using the why2 T-DNA insertion mutant and a novel knockout mutant prepared by CRISPR Cas9 mediated genome editing, this study revealed that WHIRLY2 is crucial in protecting mitochondrial DNA (mtDNA) integrity during salt stress...

Chlorambucil (Cbl) is a DNA alkylating drug in the nitrogen mustard family, but the clinical applications of nitrogen mustard antitumor drugs are frequently limited by their poor aqueous solubility, poor cellular uptake, lack of targeting, and severe side effects. Additionally, mitochondria are the energy factories for cells, and tumor cells are more susceptible to mitochondrial dysfunction than some healthy cells, thus making mitochondria an important target for tumor therapy. As a proof-of-concept, direct delivery of Cbl to tumor cells' mitochondria will probably bring about new opportunities for the nitrogen mustard family...

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction...

Mitochondria are major organelles involved in several processes related to energy supply, metabolism, and cell proliferation. The mitochondria function is transcriptionally regulated by mitochondria DNA (mtDNA), which encodes the key proteins in the electron transport chain that is indispensable for oxidative phosphorylation (OXPHOS). Mitochondrial transcriptional abnormalities are closely related to a variety of human diseases, such as cardiovascular diseases, and diabetes. The mitochondria transcription is regulated by the mtDNA, mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERFs)...

Polycystic ovary syndrome (PCOS) refers to an endocrine disorder syndrome that are correlated with multiple organs and systems. PCOS has an effect on women at all stages of their lives, and it has an incidence nearly ranging from 6% to 20% worldwide. Mitochondrial dysfunctions (e.g., oxidative stress, dynamic imbalance, and abnormal quality control system) have been identified in patients and animal models of PCOS, and the above processes may play a certain role in the development of PCOS and its associated complications...

A common feature of human aging is the acquisition of somatic mutations, and mitochondria are particularly prone to mutation due to their inefficient DNA repair and close proximity to reactive oxygen species, leading to a state of mitochondrial DNA heteroplasmy. Cross-sectional studies have demonstrated that detection of heteroplasmy increases with participant age, a phenomenon that has been attributed to genetic drift. In this first large-scale longitudinal study, we measured heteroplasmy in two prospective cohorts (combined n=1405) at two timepoints (mean time between visits, 8...

PURPOSE: Both aging and neurodegenerative illnesses are thought to be influenced by mitochondrial malfunction and free radical formation. Deformities of the energy metabolism, mitochondrial genome polymorphisms, nuclear DNA genetic abnormalities associated with mitochondria, modifications of mitochondrial fusion or fission, variations in shape and size, variations in transit, modified mobility of mitochondria, transcription defects, and the emergence of misfolded proteins associated with mitochondria are all linked to Parkinson's disease...

Mitochondria and the endoplasmic reticulum (ER) utilise unique unfolded protein response (UPR) mechanisms to maintain cellular proteostasis. Heat shock proteins (HSPs) are UPR chaperones induced by specific stressors to promote protein folding. Previous research has successfully employed transgenic reporters in Caenorhabditis elegans to report HSP induction. However, transgenic reporters are overexpressed and only show promoter regulation and not post-transcriptional regulation. To examine endogenous HSP regulation, we attempted to generate and validate endogenous reporters for mitochondrial ( HSP-60 ) and ER ( HSP-4 ) chaperones...

Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties...

Dual suppression of oxidative phosphorylation (OXPHOS) and glycolysis can disrupt metabolic adaption of cancer cells, inhibiting energy supply and leading to successful cancer therapy. Herein, we have developed an α-tocopheryl succinate (α-TOS)-functionalized iridium(III) complex Ir2, a highly lipophilic mitochondria targeting anticancer molecule, could inhibit both oxidative phosphorylation (OXPHOS) and glycolysis, resulting in the energy blockage and cancer growth suppression. Mechanistic studies reveal that complex Ir2 induces reactive oxygen species (ROS) elevation and mitochondrial depolarization, and triggers DNA oxidative damage...