bims-polgdi Biomed News
on POLG disease
Issue of 2025–08–24
twenty papers selected by
Luca Bolliger, lxBio
  1. High tide or low tide: the transport and metabolism of mitochondrial nucleotides.
  2. Mitochondrial Quality Control in Health and Disease.
  3. Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.
  4. Patent highlights December 2023-January 2024.
  5. Mitochondrial protection role of oxidoreductase-like domain containing 1 in myocardial cells under hypoxia.
  6. Unveiling the enigma: Investigating the controversy surrounding mitochondrial DNA copy number and gastric cancer using Mendelian randomization analysis.
  7. Deciphering the Molecular Dialogue: Mitochondria, Epigenetics, and Extracellular Vesicles in Placental Function and Pregnancy Complications.
  8. Diagnosing Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome in a Young Adult Female Patient With Seizures and Lactic Acidosis.
  9. Mitochondria as a Therapeutic Target in Neurodegeneration: Strategies for Restoring Cellular Homeostasis.
  10. Mitochondrial genome copy number variation across tissues in mice and humans.
  11. Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer's disease.
  12. Mitochondrial transplants make healthy babies.
  13. Community-Driven Copy Number Variant Discovery at Scale: Results from a Rare Disease Genomics Hackathon.
  14. Effect of Imeglimin on mitochondrial function in patients with type 2 diabetes mellitus: a prospective cohort study.
  15. Progress in stem cells mitochondrial proteomics research: A review.
  16. Bioelectricity in Morphogenesis.
  17. Amphipathic Proline-Rich Cell Penetrating Peptides for Targeting Mitochondria.
  18. Clinical Status of Exosomes: A Review.
  19. Xia-Gibbs syndrome in an 18-Year-Old Iranian girl: a case study of clinical features and genetic mutation.
  20. Parental Experiences of Receiving a Rare Genetic Disease Diagnosis for Their Child on Diagnosis Day.
  1. Biochem J. 2025 Aug 18. pii: BCJ20253237. [Epub ahead of print]482(16):
    High tide or low tide: the transport and metabolism of mitochondrial nucleotides.
    Thomas MacVicar.
      Mitochondria are multifaceted organelles that support numerous cellular metabolic pathways, including the biosynthesis of nucleotides required for cell growth and proliferation. Owing to an ancient endosymbiotic origin, mitochondria contain multiple copies of their own genome and therefore demand sufficient (deoxy)nucleotides in the mitochondrial matrix for DNA replication and transcription into RNA. Disturbed mitochondrial deoxynucleotide homeostasis can lead to a decline in mitochondrial DNA abundance and integrity, causing mitochondrial diseases with diverse and severe symptoms. Mitochondrial nucleotides are not only required for nucleic acid synthesis but also for bioenergetics and mitochondrial enzymatic activity. This review first explores how mitochondria supply energy and anabolic precursors for nucleotide synthesis and how the mitochondrial network influences the spatial control of cellular nucleotide metabolism. Then follows an in-depth discussion of the mechanisms that supply mitochondria with sufficient and balanced nucleotides and why these mechanisms are relevant to human mitochondrial disease. Lastly, the review highlights the emergence of regulated mitochondrial nucleotide supply in physiological processes including innate immunity and discusses the implications of dysregulated mitochondrial and cytosolic nucleotide homeostasis in pathophysiology.
    Keywords:  metabolism; mitochondria; mitochondrial disease; nucleotide salvage; nucleotide transport; nucleotides
    DOI:  https://doi.org/10.1042/10.1042/BCJ20253237
  2. MedComm (2020). 2025 Aug;6(8): e70319
    Mitochondrial Quality Control in Health and Disease.
    Lin Ye, Xinzhi Fu, Qi Li.
      Mitochondria are central regulators of cellular energy metabolism, and their functional integrity is essential for maintaining cellular homeostasis. Mitochondrial quality control (MQC) encompasses a coordinated network of mitochondrial biogenesis, dynamics (fusion and fission), and selective autophagy (mitophagy), which together sustain mitochondrial structure and function. Under physiological conditions, MQC ensures the removal of dysfunctional mitochondria, restricts excessive reactive oxygen species production, and modulates apoptosis, thereby supporting the high energy demands of organs such as the heart and brain. Disruption of MQC contributes to the onset and progression of various diseases, including neurodegenerative disorders, cardiovascular pathologies, and metabolic syndromes, largely through accumulation of damaged mitochondria and impaired metabolic signaling. While the core components of MQC have been characterized, the mechanistic interplay among its modules and their disease-specific alterations remain incompletely defined. This review provides an integrated overview of the molecular pathways governing mitochondrial biogenesis, dynamics, and mitophagy, with a focus on their cross-talk in maintaining mitochondrial homeostasis. We further discuss how MQC dysfunction contributes to disease pathogenesis and examine emerging therapeutic approaches aimed at restoring mitochondrial quality. Understanding the regulatory logic of MQC not only elucidates fundamental principles of cellular stress adaptation but also informs novel strategies for disease intervention.
    Keywords:  disease intervention; mitochondria; mitochondrial quality control; therapeutic strategies
    DOI:  https://doi.org/10.1002/mco2.70319
  3. Reprod Med Biol. 2025 Jan-Dec;24(1):24(1): e12672
    Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.
    Sanath Udayanga Kankanam Gamage, Yoshiharu Morimoto.
       Background: Mitochondria play a critical role in cellular bioenergetics and signaling, with particular importance in the context of reproductive biology. This review summarizes their role in reproduction and explores current and emerging mitochondrial therapies for fertility treatment.
    Methods: A comprehensive literature search using terms like mitochondria, infertility, reproduction, gametes, mitochondrial replacement, and mitochondrial transplantation identified relevant studies on mitochondria's role in gametogenesis, fertilization, and early embryonic development in relevant databases. Selected publications were reviewed and summarized to present current and future mitochondrial therapies for fertility.
    Main Findings: Mitochondrial dynamics and functions are critical for meeting the energy requirements of essential reproductive processes, including gametogenesis, fertilization, and early embryonic development. Dysregulation of mitochondrial function has been associated with a range of reproductive disorders, such as infertility, recurrent pregnancy loss, and maternally inherited mitochondrial diseases. Emerging therapeutic strategies, such as mitochondrial replacement therapy, antioxidant supplementation, and mitochondrial transplantation, offer promising avenues for overcoming these challenges and improving reproductive outcomes.
    Conclusions: Utilizing mitochondrial-based therapies represents a promising and innovative approach in the advancement of fertility treatments. Ongoing research and clinical development in this area hold significant potential to enhance reproductive outcomes and improve the quality of life for individuals and couples facing fertility challenges.
    Keywords:  ascent; infertility; mitochondria; mitochondrial dysfunction; mitochondrial therapies for infertility; mitochondrial transplantation; reproductive aging
    DOI:  https://doi.org/10.1002/rmb2.12672
  4. Pharm Pat Anal. 2024 ;13(4-6): 105-110
    Patent highlights December 2023-January 2024.
    Hermann Am Mucke.
      A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
    Keywords:  G-quadruplexes; cell cycle proteins; machine learning; memory T-cells; mitochondrial diseases; neuroglobin
    DOI:  https://doi.org/10.1080/20468954.2024.2390353
  5. Med Gas Res. 2026 Jun 01. 16(2): 116-124
    Mitochondrial protection role of oxidoreductase-like domain containing 1 in myocardial cells under hypoxia.
    Yan Yan, Min Dong, Liuyang Tian, Chao Zhu, Xiaojing Zhao.
      JOURNAL/mgres/04.03/01612956-202606000-00006/figure1/v/2025-08-18T154854Z/r/image-tiff Although mitochondria and related proteins are essential for mitochondrial preservation, the functions of some of these proteins remain unknown. The novel protein oxidoreductase-like domain containing 1 (OXLD1/C17orf90, UniProtKB Q5BKU9) have attracted our attention because of its correlation with mitochondria. This study revealed a decrease in OXLD1 levels in cardiomyocytes cultured in 1% oxygen for 24 hours. Suppressing OXLD1 increases mitochondrial injury under both normoxic and hypoxic conditions. This is evidenced by decreased mitochondrial membrane potential and increased reactive oxygen species production. Meanwhile, suppressing OXLD1 decreased mitochondrial oxidative phosphorylation. Overexpression of OXLD1 decreased mitochondrial injury under normoxia and hypoxia, as indicated by an increase in the mitochondrial membrane potential and a decrease in reactive oxygen species production. Moreover, overexpression of OXLD1 enhanced mitochondrial oxidative phosphorylation. Additionally, we found that OXLD1 regulates mitochondrial oxidative phosphorylation by affecting mitochondrial complexes I and V. OXLD1 plays a crucial role in protecting cardiomyocytes by improving mitochondrial function under low-oxygen conditions. OXLD1 achieves this protection through interactions with mitochondrial complexes I and V. Therefore, OXLD1 may serve as a new and important regulator of mitochondrial function.
    Keywords:  C17orf90; MMP; OXLD1; ROS; cardiomyocytes; hypoxia; mitochondria; mitochondrial complex I; mitochondrial complex V; oxidative phosphorylation
    DOI:  https://doi.org/10.4103/mgr.MEDGASRES-D-24-00117
  6. Medicine (Baltimore). 2025 Aug 15. 104(33): e43916
    Unveiling the enigma: Investigating the controversy surrounding mitochondrial DNA copy number and gastric cancer using Mendelian randomization analysis.
    Jie Zhou, Taohua Shangguan, Yixin Xu, Chao Chen, Kun Wang.
      Gastric cancer (GC), as one of the most prevalent malignant tumors, significantly impacts individuals' health. Many studies have examined the relationship between mitochondrial DNA (mtDNA) copy number and GC. However, conclusions remain inconclusive, with conflicting findings. The genome-wide association study summary statistics for mtDNA copy number were obtained from 2 sources: one from a robust cohort of 465,809 White individuals provided by the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the UK Biobank; and the other from a dataset comprising 395,718 UK Biobank participants. In addition, a total of 5 sets of genome-wide association study summary statistics for GC were obtained through datasets from Finland, the European Bioinformatics Institute, and the Integrative Epidemiology Unit at the University of Bristol, encompassing a total of 937,663 participants. Furthermore, we undertook a 2-sample bidirectional Mendelian randomization analysis to explore the association between mtDNA copy number and GC. The Inverse variance weighted (IVW) method was primarily utilized, complemented by 4 other validation methods. Based on our comprehensive investigation, no discernible causal relationship was found between mtDNA copy number and GC in both the training and validation cohorts (IVW, P >.05). Furthermore, in the reverse Mendelian randomization analysis, no association was observed between GC and mtDNA copy number either (IVW, P >.05). Additionally, all analyses showed no evidence of horizontal pleiotropy or heterogeneity. The findings of this study provide evidence that there is no causal relationship between mtDNA copy number and GC.
    Keywords:  GWAS; causal relationship; genetically predicted; single nucleotide polymorphism
    DOI:  https://doi.org/10.1097/MD.0000000000043916
  7. Compr Physiol. 2025 Aug;15(4): e70040
    Deciphering the Molecular Dialogue: Mitochondria, Epigenetics, and Extracellular Vesicles in Placental Function and Pregnancy Complications.
    Yu-Chin Lien, Rebecca A Simmons.
      Placental dysfunction is implicated in the pathogenesis of multiple pregnancy complications. Mitochondria are the powerhouse of the cell and are critical for placental metabolism and function. Several pregnancy complications are associated with oxidative stress and mitochondrial alterations. Mitochondrial function is also essential for epigenetic modifications, which are pivotal in regulating gene expression during pregnancy. Extracellular vesicles (EVs) carry and transfer a variety of biological molecules, including intact mitochondria and mitochondrial components, and act as modifiers of epigenetics in recipient cells. Changes in the EV profile may serve as biomarkers for pregnancy complications. In the present review, we summarize the associations of mitochondrial dysfunction, epigenetic alterations, and changes in EVs that are associated with pregnancy complications. We also describe the link between mitochondria and epigenetics, mitochondria in EVs, and EVs in epigenetic modifications, which provide insight into the possible implications of crosstalk among mitochondria, epigenetics, and EVs in regulating placental function and adverse pregnancy outcomes.
    DOI:  https://doi.org/10.1002/cph4.70040
  8. Cureus. 2025 Jul;17(7): e88031
    Diagnosing Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome in a Young Adult Female Patient With Seizures and Lactic Acidosis.
    Ishan A Sane, Jessica R Gupte.
      The aim of this case report is to highlight the diagnostic challenges and clinical presentation of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, which is a rare, maternally inherited mitochondrial disorder. MELAS typically manifests with a constellation of neurological and systemic symptoms, including seizures, lactic acidosis, stroke-like episodes, and progressive cognitive decline. Mutations in mitochondrial DNA impair oxidative phosphorylation and result in widespread cellular dysfunction. We report the case of a 33-year-old female patient who presented with seizures, altered mental status, and focal neurological deficits. Laboratory evaluation revealed elevated serum lactate, and neuroimaging demonstrated stroke-like lesions not confined to vascular territories. A muscle biopsy showed abnormal mitochondrial accumulation, and electron microscopy detected ragged red fibers, which is confirmatory of mitochondrial cytopathy. The patient was managed symptomatically in the intensive care unit with antiepileptics, corticosteroids, and a mitochondrial cocktail comprising coenzyme Q10, L-arginine, L-carnitine, and B-complex vitamins. Plasmapheresis was also performed during initial management due to diagnostic uncertainty. The patient showed gradual clinical improvement and was discharged on supportive therapy. This case emphasizes the importance of early recognition of atypical stroke-like presentations and metabolic derangements in young patients. MELAS syndrome should be considered in the differential diagnosis of stroke mimics, especially in the absence of vascular risk factors. Timely diagnosis, supportive care, and long-term follow-up, including genetic counselling, are essential for optimizing outcomes in these patients.
    Keywords:  encephalomyopathy; lactic acidosis; melas syndrome; mitochondrial disorder; red ragged fibers; stroke-like episodes
    DOI:  https://doi.org/10.7759/cureus.88031
  9. Curr Neuropharmacol. 2025 Aug 12.
    Mitochondria as a Therapeutic Target in Neurodegeneration: Strategies for Restoring Cellular Homeostasis.
    Bartosz Twarowski, Iwona Piątkowska-Chmiel, Mariola Herbet.
      Ageing is a complex biological process marked by a gradual decline in bodily functions at the cellular, tissue, and organ levels, resulting from molecular damage and environmental influences. It increases disease risk, particularly in older adults with neurodegenerative conditions characterized by progressive neuronal loss and neurological symptoms such as cognitive and motor impairments. Key mechanisms include abnormal protein accumulation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Disruption of cellular homeostasis prevents the maintenance of internal conditions such as pH and glucose levels. Mitochondria, known as the cell's "powerhouses," are essential for ATP production, DNA protection, and metabolic regulation, supporting cellular structures. Their dysfunction plays a crucial role in the progression of neurodegenerative diseases. Factors like chronic inflammation, ATP deficiency, excessive production of reactive oxygen species (ROS), and calcium imbalance leads to oxidative stress and neuronal damage, exacerbating neurodegeneration. Current therapies mainly focus on symptom relief, emphasizing the urgent need for new treatment strategies. Given the key role of mitochondrial dysfunction, therapies aiming to restore mitochondrial homeostasis are gaining increasing attention. Mitochondrial antioxidants such as MitoQ, MitoTEMPO, and SkQ1 have shown neuroprotective, anti-inflammatory, and antioxidant properties. Research into their therapeutic potential may lead to the development of effective drugs that restore mitochondrial function and improve quality of life of the patienst.
    Keywords:  Mitochondrial antioxidants; mitochondrial dysfunction.; neurodegenerative diseases; neuropharmacology; toxicology
    DOI:  https://doi.org/10.2174/011570159X389970250727031306
  10. Proc Natl Acad Sci U S A. 2024 Aug 13. 121(33): e2402291121
    Mitochondrial genome copy number variation across tissues in mice and humans.
    Sneha P Rath, Rahul Gupta, Ellen Todres, Hong Wang, Alexis A Jourdain, Kristin G Ardlie, Sarah E Calvo, Vamsi K Mootha.
      The mammalian mitochondrial genome (mtDNA) is multicopy and its copy number (mtCN) varies widely across tissues, in development and in disease. Here, we systematically catalog this variation by assaying mtCN in 52 human tissues across 952 donors (10,499 samples from the Genotype-Tissue Expression project) and 20 murine tissues using qPCR, capturing 50- and 200-fold variation, respectively. We also estimate per cell mtCN across 173 human cell lines from the Cancer Cell Line Encyclopedia using whole-genome sequencing data and observe >50-fold variation. We then leverage the vast amount of genomics data available for these repositories to credential our resource and uncover mtDNA-related biology. Using already existing proteomics data, we show that variation in mtCN can be predicted by variation in TFAM, histone, and mitochondrial ribosome protein abundance. We also integrate mtCN estimates with the CRISPR gene dependency measurements to find that cell lines with high mtCN are resistant to loss of GPX4, a glutathione phospholipid hydroperoxidase. Our resource captures variation in mtCN across mammalian tissues and should be broadly useful to the research community.
    Keywords:  GPX4; TFAM; histone; mitochondrial ribosome; mtDNA
    DOI:  https://doi.org/10.1073/pnas.2402291121
  11. Mitochondrion. 2025 Aug 15. pii: S1567-7249(25)00074-1. [Epub ahead of print] 102077
    Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer's disease.
    Tulika Gupta, Asha Rao, Veena Devi, Lalita Kumari, Akshita Negi, Munish Kumar, Ranjana Bharti, Bikash Medhi.
      Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), contributing to cognitive decline. This study explores the therapeutic potential of mitochondrial transplantation in mitigating cognitive decline in AD. Structurally and functionally characterized mitochondria from young rat brains were intravenously transplanted into AD rats. Confocal imaging confirmed integration of exogenous tagged mitochondria into hippocampal tissue. Post-mitotherapy, we noted significant cognitive improvement by neurobehavioral tests and significant reduction in protein levels of amyloid precursor protein. Further mitochondrial functional parameters improved; reduced oxidative stress, improved mitochondrial membrane potential, and calcium homeostasis. These findings highlight mitotherapy as a promising strategy for treating Alzheimer's disease.
    Keywords:  AD Rat model; Alzheimer’s disease (AD); Cognitive improvement; Mitochondrial dysfunction; Mitotherapy
    DOI:  https://doi.org/10.1016/j.mito.2025.102077
  12. Nat Biotechnol. 2025 Aug 19.
    Mitochondrial transplants make healthy babies.
    Laura DeFrancesco.
      
    DOI:  https://doi.org/10.1038/s41587-025-02799-2
  13. medRxiv. 2025 Aug 12. pii: 2025.08.08.25333317. [Epub ahead of print]
    Community-Driven Copy Number Variant Discovery at Scale: Results from a Rare Disease Genomics Hackathon.
    Ming Yin Lun, Jennifer E Posey, Jesse D Bengtsson, Haowei Du, Rituparna Sinha Roy, Lei Yang, Sebastian Ochoa, Bo Yuan, Maddie Gillentine, Anna Lindstrand, Claudia M B Carvalho.
       Purpose: Copy number variants (CNVs) are a major contributor to rare genetic diseases, but their detection and interpretation from short-read genome sequencing (srGS) data remain challenging, especially at scale. Large amounts of existing srGS data remain under-analyzed for clinically relevant CNVs.
    Methods: During a collaborative Hackathon, we developed and applied scalable CNV analysis workflows to srGS data from three unsolved, exome-negative, rare disease cohorts: Primary Immunodeficiency (N = 39), Turkish developmental disorders (N = 31), and data from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) (N = 1437). We employed Parliament2 for structural variant (SV) calling, Mosdepth and SLMSuite for read-depth-based quality control and CNV detection, and R Shiny-based visualization tools. We also constructed an SV/CNV variant database with population frequency and pathogenicity annotations, applied DBSCAN clustering for internal allele frequency estimation, and used a 3-way annotation strategy to aid interpretation.
    Results: Our pipelines identified high-confidence CNVs and streamlined interpretation across cohorts. Within 2 days, the Hackathon yielded 39 candidate pathogenic SVs. The tools and workflows enabled rapid filtering, prioritization, and visualization of clinically relevant variants.
    Conclusion: This community-driven effort demonstrates the feasibility and utility of scalable CNV analysis for accelerating diagnosis and discovery in rare disease cohorts using srGS data.
    DOI:  https://doi.org/10.1101/2025.08.08.25333317
  14. Front Endocrinol (Lausanne). 2025 ;16 1585834
    Effect of Imeglimin on mitochondrial function in patients with type 2 diabetes mellitus: a prospective cohort study.
    Abhishek Satheesan, Janardanan Kumar, Kakithakara Vajravelu Leela, Ria Murugesan.
       Background: Imeglimin, a novel oral hypoglycemic agent, is known to influence mitochondrial function and glucose metabolism. This study evaluates its effects on glycemic control, mitochondrial DNA (mtDNA) copy number, and telomere dynamics in type 2 diabetes mellitus (T2DM).
    Methods: Type 2 diabetes mellitus patients were assigned to one of four treatment groups: (1) Imeglimin alone, (2) Imeglimin with metformin, (3) Imeglimin with other oral hypoglycemic agents, and (4) Metformin with other oral hypoglycemic agents. Clinical and metabolic parameters, mtDNA copy number, and relative telomere length were assessed at baseline and six months. Statistical analyses included paired t-tests and mixed models.
    Results: The study included participants with a mean age of 55.6 years (57% male, BMI 28.8 kg/m2). HbA1c significantly decreased in the Imeglimin + Other OHA (p < 0.001), Imeglimin + Metformin (p < 0.001), and Metformin + Other OHA (p < 0.001) groups, with a smaller but significant decrease in the Imeglimin monotherapy group (p = 0.04). mtDNA copy number increased significantly in the Imeglimin-based combination groups (p < 0.05) but not with monotherapy (p = 0.18). No serious adverse events were reported. Relative telomere length was only associated with age and changes in LDL-c levels.
    Conclusion: Imeglimin-based combination therapy effectively improves glycemic control and mitochondrial function, while monotherapy offers limited benefits. Combination therapy may be preferable for optimizing metabolic outcomes in T2DM. No significant change in telomere length was observed during the short period of time.
    Keywords:  Imeglimin; glycemic control; mitochondrial DNA; telomere length; type 2 diabetes
    DOI:  https://doi.org/10.3389/fendo.2025.1585834
  15. Adv Clin Exp Med. 2025 Aug 19.
    Progress in stem cells mitochondrial proteomics research: A review.
    Weidong Yao, Xinyi Yu, Yameng Wang, Liang Xia.
      This review summarizes the latest advancements in stem cell (SC) mitochondrial proteomics. With the rapid development of biotechnology, mitochondrial proteomics has emerged as a pivotal area in SC research. The research methods used in mitochondrial proteomics include mass spectrometry (MS), with pre-MS sample processing, MS data acquisition employing both qualitative and quantitative approaches, and bioinformatics analysis to annotate and explore protein functions. In recent years, mitochondrial proteomics research has contributed to the establishment and expansion of our understanding of the roles of various mitochondrial proteins involved in regulating SC differentiation, metabolism and aging, including Drp1, Mfn1/2, OPA1, SIRT3, Bcl-2, YME1L, and PGC-1α. This multidisciplinary approach, combining qualitative and quantitative proteomics with bioinformatics, sheds light on the intricate regulatory mechanisms of mitochondrial proteins in SC. These findings provide a scientific basis for developing novel therapeutic targets and strategies, thereby advancing the field of regenerative medicine and personalized treatment paradigms.
    Keywords:  bioinformatics; mass spectrometry; mitochondria; proteomics; stem cells
    DOI:  https://doi.org/10.17219/acem/203862
  16. Annu Rev Cell Dev Biol. 2025 Aug 19.
    Bioelectricity in Morphogenesis.
    Custodio O Nunes, Elias H Barriga.
      Bioelectricity is likely as old as life itself. From the moment the first proto-cell was enclosed in a lipid bilayer, a membrane potential arose. Thus, one can expect that bioelectrical activities influence single-cell and collective cell behaviors in processes such as embryo development, tissue repair, and even disease. Despite the ubiquity of bioelectrical phenomena, most research has focused on bioelectrical control of neural tissues, and as a result, our knowledge of nonneural contexts remains comparatively less understood, scattered, and often misunderstood. Still, there are strong reasons for supporting the idea that bioelectricity contributes to diverse morphogenetic contexts. Thus, in this review we provide an overview of the current knowledge of how cells generate and perceive bioelectrical inputs, and discuss how cells translate these stimuli into responses that influence tissue morphogenesis in physiology and pathology.
    DOI:  https://doi.org/10.1146/annurev-cellbio-101323-032747
  17. ACS Chem Biol. 2025 Aug 18.
    Amphipathic Proline-Rich Cell Penetrating Peptides for Targeting Mitochondria.
    Adeline Schmitt, Helma Wennemers.
      Cell-penetrating peptides (CPPs) offer a platform for targeted intracellular delivery. Here, we developed amphipathic oligoprolines for targeting mitochondria. The rigid peptides feature cationic guanidinium and hydrophobic cyclohexyl groups aligned along the edges of the polyproline II (PPII) helical backbone. Systematic variations of the hydrophobicity through C-terminal and backbone modifications provided CPPs with enhanced cellular uptake and mitochondrial selectivity. Comparative studies with conformationally more flexible analogs revealed the benefit of aligned cationic and hydrophobic residues on a rigid backbone for mitochondria targeting. Notably, the amphipathic peptides undergo time-dependent intracellular redistribution, leading to selective and prolonged mitochondrial residency. Our findings established design principles for optimizing CPPs to target mitochondria.
    DOI:  https://doi.org/10.1021/acschembio.5c00479
  18. HSS J. 2025 Aug 16. 15563316251362179
    Clinical Status of Exosomes: A Review.
    Jonathan Sgaglione, Eric V Neufeld, Pooja Swami, Daniel A Grande.
      Nano-sized extracellular vesicles enclosed by a lipid bilayer and secreted by various cell types including mesenchymal stem cells, exosomes act as natural transporters, carrying bioactive molecules such as proteins, lipids, and nucleic acids that mediate intercellular communication. Exosomes influence a range of cellular processes, including immune modulation, tissue repair, and disease progression. Compared to whole-cell therapies, exosomes provide anti-inflammatory, immunosuppressive, and regenerative effects with reduced risks linked to cellular components, such as infusion toxicity, immunogenicity, and tumorigenic phenomena. This article reviews isolation, modification, characterization, and storage techniques, challenges in clinical translation, and innovative engineering strategies to enhance targeting and efficacy. It also examines preliminary evidence suggesting that exosomes may have potential in managing degenerative disorders such as osteoarthritis, intervertebral disc degeneration, osteoporosis, osteonecrosis, and tendinopathy, as well as non-degenerative disorders such as sciatic nerve injury, fractures, and soft tissue trauma.
    Keywords:  extracellular vesicle; mesenchymal stem cells; regenerative medicine; stem cells
    DOI:  https://doi.org/10.1177/15563316251362179
  19. Mol Biol Rep. 2025 Aug 18. 52(1): 834
    Xia-Gibbs syndrome in an 18-Year-Old Iranian girl: a case study of clinical features and genetic mutation.
    Mohadese Farahani, Amir Jalali, Mobina Ebrahimi, Hossein Kazemi.
       BACKGROUND: Xia-Gibbs syndrome (XGS) is a rare, autosomal dominant genetic disorder characterized by a broad spectrum of neurological, motor, and developmental symptoms. This study presents the first reported case of XGS in Iran involving an 18-year-old girl with diverse clinical manifestations, including developmental delay, motor disorders, delayed puberty, and behavioral disturbances. Genetic analysis identified a de novo nonsense mutation in the AHDC1 gene (c.2062 C > T, p.(Arg688Ter)), resulting in a truncated and non-functional protein, which correlates with the patient's symptoms.
    CONCLUSION: This case underscores the importance of early and accurate diagnosis of XGS and highlights the need for increased awareness among healthcare professionals, particularly in rare genetic disorders. Reporting such cases is crucial for enhancing understanding of the disease mechanisms and improving patient management.
    Keywords:   AHDC1 ; Delayed puberty; Motor disorders; Neurological disorders; Xia-Gibbs syndrome
    DOI:  https://doi.org/10.1007/s11033-025-10933-1
  20. Am J Med Genet A. 2025 Aug 17. e64223
    Parental Experiences of Receiving a Rare Genetic Disease Diagnosis for Their Child on Diagnosis Day.
    Isabel Bullock, Kristen Fishler Malone, Abigail Turnwald.
      Literature exploring the experiences of parents of children with rare genetic conditions on "Diagnosis Day," the day a diagnosis is given, is limited. We created a survey to further explore these experiences. Parents of children with rare genetic conditions 18 years or younger were recruited through rare disease organizations and social media. Seven hundred and seventeen participants, representing 229 rare diseases, met the inclusion criteria. Most parents received their child's diagnosis in person. Other parents received the diagnosis by phone or telehealth. Most parents (73%) were satisfied with where the diagnosis was given. Parents experienced a range of emotions on Diagnosis Day, most commonly hopelessness, sadness, confusion, and relief. With a longer time to diagnosis, participants reported more positive emotions and fewer negative emotions (p < 0.001). The information parents considered most important on Diagnosis Day included details about quality of life, medical management, inheritance, and connecting with other families. Nearly half of parents felt that providers could have done something different when delivering the diagnosis, including providing specific information on the diagnosis, asking parents to decide where results are given, asking about including other family members, and providing compassion and empathy. Together, these findings can be used to improve the Diagnosis Day experience for parents.
    Keywords:  diagnosis day; genetic diagnosis; genetic testing; rare disease; result disclosure
    DOI:  https://doi.org/10.1002/ajmg.a.64223
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