bims-ripira Biomed News
on RRM2B MDMD in Adults
Issue of 2026–07–05
eleven papers selected by
Martín Lopo
  1. Analysis of whole-exome sequencing data from nearly 10,000 Iranian individuals: identification of recessive mitochondrial disease variants and proposal of a population-specific carrier screening panel.
  2. Acupuncture-driven exosomes: an emerging therapy.
  3. The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease.
  4. Pearson syndrome: expanding the clinical spectrum of a mitochondrial cytopathy-a case report.
  5. [Mitochondrial diseases].
  6. Crosstalk in the kidney-muscle axis: myokines and muscle-relevant mediators in chronic kidney disease-associated sarcopenia.
  7. [Uric acid and mitochondrial dysfunction: a review].
  8. [Is it possible to generate artificial mitochondrial genome?]
  9. Advancing the monitoring of organelle contact sites in vitro and in vivo.
  10. A de novo TWNK Variant Mimicked Sporadic Chronic Progressive External Ophthalmoplegia.
  11. Systems modelling of mitochondrial dynamics in different exercise regimes.
  1. Hum Genomics. 2026 Jun 30.
    Analysis of whole-exome sequencing data from nearly 10,000 Iranian individuals: identification of recessive mitochondrial disease variants and proposal of a population-specific carrier screening panel.
    Mohadeseh Fathi, Parvaneh Karimzadeh, Farzad Ahmadabadi, Damoun Nashta Ali, Narjes Jafari, Raheleh Tangestani, Shadab Salehpour, Toktam Moosavian, Soudeh Ghafouri-Fard, Mohammad Miryounesi.
       BACKGROUND: Mitochondrial diseases, often stemming from recessive nuclear gene mutations, represent a heterogeneous group of disorders with significant morbidity and mortality. Carrier screening for these conditions is population-specific, yet data on the pathogenic variant burden in the Iranian population remain limited. This study aimed to analyze whole-exome sequencing (WES) data from 9989 Iranian individuals to identify the spectrum and frequency of recessive mitochondrial disease variants and to develop a population-specific carrier screening panel.
    METHODS: We analyzed WES data from 9989 unrelated Iranian individuals. Variants in 1,564 nuclear genes associated with mitochondrial function were filtered for rarity (minor allele frequency < 0.01 in public databases), predicted pathogenicity, and recessive inheritance patterns (homozygous or compound heterozygous). Clinically relevant variants were manually curated, and carrier frequencies for significant recessive mitochondrial conditions were calculated.
    RESULTS: Our analysis identified variants across 15 groups of mitochondrial-related nuclear genes in 345 individuals recognized as carriers. Of these, 123 variants (35.6%) were classified as Pathogenic, and 154 variants (44.6%) were classified as Likely Pathogenic according to ACMG guidelines.
    CONCLUSIONS: This study provides the first large-scale WES-derived assessment of recessive mitochondrial disease carrier burden in the Iranian population. The high estimated carrier rate supports implementing population-specific preconception screening. The results of this study can be used for design of targeted panels of nuclear mitochondrial genes to identify at-risk couples, facilitating genetic counseling and reproductive decision-making in Iran.
    Keywords:  Carrier frequency; Mitochondrial disorders; Whole exome sequencing
    DOI:  https://doi.org/10.1186/s40246-026-01011-z
  2. J Tradit Chin Med. 2026 Jun;46(3): 768-778
    Acupuncture-driven exosomes: an emerging therapy.
    Jian Jiawei, Ding Zhimin, Zhuang Yueyang, Wang Junzi, Yang Minguang, Liu Weilin.
      Acupuncture, as a significant component of Traditional Chinese Medicine (TCM), has attracted increased attention for its mechanism of controlling the physiological functions of the human body and promoting the recovery of diseases by stimulating specific acupoints. Despite its long history and wide clinical application, the mechanism of action of acupuncture is still not fully understood. More research needs to be done on how acupuncture affects molecular communication and cellular function. Exosomes are nanoscale vesicles that rely on cellular multivesicular bodies (MVBs) fused with cell membranes to be released into the extracellular matrix. They are crucial for information transfer between cells and are currently a hot research topic in the world's cutting-edge life sciences. Previous research has demonstrated that the therapeutic effect of acupuncture may be related to stimulating certain cells to secrete exosomes, that exosomes released may contain "acupuncture information", and that manipulating the back-injection of exosomes to produces "acupuncture-like" effects. These findings suggest that exosomes could serve as a bridge between conventional acupuncture therapy and modern precision medicine. They also offer fresh prospects and difficulties for acupuncture translational medicine research. To better define the relationship between exosomes and acupuncture, we reviewed and systematized the literature on past studies related to exosomes and acupuncture. This paper provides a significant theoretical and experimental foundation for applying exosomes in precision medicine by summarizing and analyzing the relationship between acupuncture stimulation and exosome function. This is expected to promote the combination of traditional acupuncture therapy and modern biotechnology and bring innovation and progress to future medical practice.
    Keywords:  acupuncture; exosomes; mechanisms; medicine, Chinese traditional; network regulation; review
    DOI:  https://doi.org/10.19852/j.cnki.jtcm.2026.03.017
  3. medRxiv. 2026 Jun 15. pii: 2026.06.12.26355546. [Epub ahead of print]
    The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease.
    Johan L K Van Hove, Marisa W Friederich, Roxanne A Van Hove, Jessica C Lee, Kaz M Knight, Tonia E Donovan, Lori Silveira, Rebecca D Ganetzky, Michio Hirano, Jose Abdenur, Merlin G Butler, David Cassiman, Bruce H Cohen, Sarah H Elsea, Gregory M Enns, William A Gahl, Ralitza Gavrilova, Gabrielle C Geddes, Emma E Glamuzina, Amy Goldstein, Richard H Haas, Aneal Khan, Kimberly A Kripps, Austin A Larson, April N Lehman, Uta Lichter-Konecki, Johannes A Mayr, Eva Morava, James T Peterson, Jill A Rosenfeld, Russell P Saneto, Fernando Scaglia, Emily Shelkowitz, Mariella Simon, Joél E G Smet, Wendy E Smith, Claudia Soler-Alfonso, Mark Tarnopolsky, Rudy N A Van Coster, Arnaud V Vanlander, Pieter Vermeersch, Jerry Vockley, Kristen Wigby, Lynne A Wolfe, Saskia B Wortmann, Jennifer H Yang.
      Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.
    One sentence summary: A combination of four mitochondrial functional tests to identify or confirm suspected primary mitochondrial disease in fibroblasts had good sensitivity and excellent specificity, well beyond what was perceived using enzyme assays only.
    DOI:  https://doi.org/10.64898/2026.06.12.26355546
  4. J Med Case Rep. 2026 Jul 01.
    Pearson syndrome: expanding the clinical spectrum of a mitochondrial cytopathy-a case report.
    Alizah Faisal, Hooria Waqas, Hania Masood, Armeen Butt, Saad Rahman, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Ali Iqbal, Muhammad Usama Naveed.
       BACKGROUND: Pearson syndrome (PS) is a rare multisystem mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions (SLSMDs). It typically presents in infancy with refractory sideroblastic anemia, exocrine pancreatic insufficiency, and failure to thrive. Due to its heterogeneous manifestations and resemblance to other hematological conditions, early diagnosis remains a clinical challenge.
    CASE PRESENTATION: A south asian male infant presented with persistent pancytopenia, severe anemia unresponsive to intravenous and oral iron and multivitamin supplements, exocrine pancreatic insufficiency, failure to thrive, and metabolic acidosis. Born to consanguineous parents, the child had a significant family history of early infant deaths and hematological abnormalities. Peripheral smear showed marked anisopoikilocytosis with cytoplasmic vacuolization of erythroid precursors. Bone marrow analysis revealed erythroid hyperplasia, dyserythropoiesis, vacuolated precursors in both the erythroid and myeloid lineages, and ringed sideroblasts. Steatorrhea was consistent with exocrine pancreatic insufficiency, a recognized feature of Pearson syndrome. Although HbA1c was marginally elevated, this finding is nonspecific in infancy and does not indicate endocrine pancreatic dysfunction. Endocrine involvement is typically reported later during mitochondrial disorders and was not supported clinically or biochemically in this case. While mitochondrial DNA deletions underlying Pearson syndrome are usually sporadic, the presence of consanguinity and multiple affected siblings in this family raises the possibility of modifying nuclear genetic factors contributing to phenotypic variability. The overall constellation of clinical features, hematological findings, and bone marrow morphology was diagnostic of Pearson syndrome.
    CONCLUSIONS: This case underscores the importance of considering mitochondrial cytopathies in infants presenting with unexplained pancytopenia, multisystem involvement, and a suggestive family history, even in the presence of parental consanguinity. Early recognition, even in resource-limited settings, is vital for prognostication and family counseling, though definitive treatment remains supportive.
    Keywords:  Exocrine pancreatic insufficiency; Failure to thrive; Mitochondrial disorder; Pancytopenia; Pearson syndrome; Sideroblastic anemia; Vacuolated precursors
    DOI:  https://doi.org/10.1186/s13256-026-06288-1
  5. Ugeskr Laeger. 2026 Jun 22. pii: V10250820. [Epub ahead of print]188(26):
    [Mitochondrial diseases].
    Simone Rask Nielsen, Elsebeth Østergaard, John Vissing, Anja Lisbeth Frederiksen.
      Mitochondrial diseases are complex conditions that can affect many organs, and patients may be seen by doctors from various clinical specialities. Currently, treatments are primarily supportive; however, this review finds that identifying the underlying genetic cause is becoming increasingly important as new targeted therapies are under development. Additionally, recent advances in reproductive technologies, such as pre-implantation testing and mitochondrial replacement therapy, may offer additional options for affected patients.
    DOI:  https://doi.org/10.61409/V10250820
  6. Front Med (Lausanne). 2026 ;13 1868285
    Crosstalk in the kidney-muscle axis: myokines and muscle-relevant mediators in chronic kidney disease-associated sarcopenia.
    Ran Hu, Xuelian Zhang, Lan Hu, Xu Li, Qin Hu, Hua Jin.
      Chronic kidney disease (CKD) is a systemic disorder in which sarcopenia serves as a critical driver of frailty and mortality. However, the "kidney-muscle axis" remains conceptually fragmented, often confounded by the overlapping definitions of protein-energy wasting (PEW) and cachexia. This review argues that CKD-associated sarcopenia is not driven by isolated myokines, but rather by a clearance-distorted, inflammation-coupled signaling network. We first disambiguate sarcopenia from PEW and cachexia, distinguishing canonical myokines from mediators whose interpretive value is altered by uremia. We then propose a framework organized around four pillars: hypercatabolism, anabolic resistance, mitochondrial dysfunction and bioenergetic remodeling, and context-dependent inflammatory signaling. Within this context, we reinterpret key mediators, including myostatin, growth differentiation factor 15 (GDF-15), insulin-like growth factor 1 (IGF-1), irisin, and interleukin-6 (IL-6), emphasizing that their circulating levels reflect a complex entanglement of altered secretion, impaired renal clearance, and tissue-specific resistance. While the kidney-to-muscle vector is well-supported, direct muscle-to-kidney feedback remains less established. By framing myokine dysregulation as a mechanistic interface, this review aims to refine causal inference and support the development of targeted therapies for muscle wasting in CKD.
    Keywords:  chronic kidney disease; kidney-muscle axis; muscle wasting; myokines; protein-energy wasting; renal clearance; sarcopenia
    DOI:  https://doi.org/10.3389/fmed.2026.1868285
  7. Ter Arkh. 2026 Jun 13. 98(5): 320-324
    [Uric acid and mitochondrial dysfunction: a review].
    G V Grigorenko, V V Tsurko.
      The relationship between hyperuricemia and mitochondrial dysfunction remains poorly described in literature, despite its important clinical significance. The aim of this review is to identify the causes and mechanisms of uric acid's influence on the development of mitochondrial dysfunction. This review presents a comprehensive analysis of the pathogenetic relationship between uric acid (UA) and mitochondrial dysfunction as an evolutionarily formed process aimed at maintaining cellular energy homeostasis in conditions of energy deficiency, but modified into a pathological process in modern conditions of over-nutrition. The important role of the metabolism of fructose and its metabolite, UA, in the regulation of the energy balance of the cell is analyzed. The mechanisms of increased oxidative stress caused by UA and their effect on mitochondrial function have been determined. The important role of AMP-activated protein kinase (AMPK), a key regulator of cellular homeostasis, is analyzed, the inhibition of which by UA leads to mitochondrial dysfunction.
    Keywords:  fructose; homeostasis; hyperuricemia; mitochondrial dysfunction; uric acid
    DOI:  https://doi.org/10.26442/00403660.2026.05.203610
  8. Nihon Yakurigaku Zasshi. 2026 ;161(4): 216-221
    [Is it possible to generate artificial mitochondrial genome?]
    Ken-Ichi Wada.
      The mitochondrial genome (mtDNA) is a circular DNA of approximately 16.5 kbp, present at several thousand copies per cell. Although mtDNA is extremely small compared with the nuclear genome, it is quite important for life system because it encodes components essential for ATP production through oxidative phosphorylation. Since mtDNA mutations are thought to be implicated in a wide range of diseases, gene therapies targeting mtDNA are expected to provide promising treatment options for such disorders; however, current methods allow only limited manipulation of mtDNA. In this article, our recent efforts toward establishing mtDNA writing, a technology that would enable unrestricted and precise manipulation of mtDNA, are introduced. We hypothesized that creation of specialized host cells that preferentially accept exogenous mtDNA would be the key to achieving mtDNA writing. We named such host cells "e-mt cells" and assumed that cells maintaining a deviated type of mtDNA in a homoplasmic state could function as e-mt cells. To create e-mt cells, we developed a novel mitochondrial transfer method using a microfluidic device. This microfluidic device allowed direct and non-invasive mitochondrial transfer between live single cells by fusing them through a micro aperture (microslit/microtunnel). Furthermore, we successfully demonstrated single-mitochondrion transfer as well as cybrid generation via mitochondrial transfer into ρ0 cells. These findings suggest that the microfluidic device has the potential to achieve homoplasmic mtDNA modification through mtDNA cloning and is therefore expected to contribute to the creation of e-mt cells.
    DOI:  https://doi.org/10.1254/fpj.25090
  9. Biochem Soc Trans. 2026 Jul 29. 54(7): 887-899
    Advancing the monitoring of organelle contact sites in vitro and in vivo.
    Lucia Barazzuol, Caterina Peggion, Marisa Brini, Yusuke Nasu, Tito Calì.
      Organelle contact sites are highly dynamic and specialized regions where distinct organelles come into proximity, enabling direct inter-organelle communication. These structures play fundamental roles in cellular homeostasis by coordinating the exchange of lipids, metabolites, and ions, as well as regulating key processes such as organelle dynamics, mitochondrial fission, autophagy, and metabolic integration. Alterations in contact site architecture and function have been increasingly associated with a wide range of human diseases, including neurodegeneration, metabolic disorders, and cancer. Despite their biological relevance, the nanoscale nature and dynamic behaviour of contact sites have historically posed significant challenges for their accurate detection and functional characterization. Here, we provide a comprehensive overview of the methodologies currently available to study organelle contact sites, ranging from classical approaches such as electron microscopy and biochemical fractionation to advanced imaging techniques and genetically encoded reporters. We discuss recent developments in high-resolution and live-cell microscopy that have improved the spatial and temporal resolution of contact site analysis, as well as emerging tools designed to selectively label, quantify, and manipulate these interfaces. Attention is given to the next generation of engineered reporters capable of sensing molecular and ionic exchanges at contact sites, thereby moving beyond structural description toward functional interrogation. By critically evaluating the strengths and limitations of existing approaches, we aim to provide a framework for selecting appropriate tools and to highlight future directions in the field. Ultimately, advancing our ability to monitor and dissect organelle contact sites will be essential for understanding their contribution to cellular physiology and disease.
    Keywords:  Organelle contact sites; SPLICS; genetically encoded reporters
    DOI:  https://doi.org/10.1042/BST20250371
  10. Intern Med. 2026 Jun 27.
    A de novo TWNK Variant Mimicked Sporadic Chronic Progressive External Ophthalmoplegia.
    Chiharu Yoshida, Akatsuki Kubota, Norifumi Kawamoto, Kensuke Takahashi, Satoka Yano, Shogo Komaki, Meiko Maeda, Hiroya Naruse, Takashi Matsukawa, Masashi Hamada, Wataru Satake, Tatsushi Toda.
      Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease, with most sporadic cases caused by a single large mitochondrial DNA (mtDNA) deletion. We report the case of a 54-year-old woman with ptosis, external ophthalmoplegia, and proximal muscle weakness without any relevant family history. A muscle biopsy supported the diagnosis of sporadic CPEO. However, a muscle DNA analysis revealed multiple mitochondrial DNA (mtDNA) deletions. Whole-exome sequencing identified a heterozygous pathogenic TWNK variant [c.1121G>A (p.Arg374Gln)] absent in her parents, suggesting a de novo origin. Although TWNK pathogenic variants typically cause autosomal dominant CPEO, this case mimicked a sporadic form, thus highlighting the importance of a nuclear gene analysis in such cases.
    Keywords:  TWNK; chronic progressive external ophthalmoplegia; de novo variant; mitochondrial disease
    DOI:  https://doi.org/10.2169/internalmedicine.7395-26
  11. J Physiol. 2026 Jul 01.
    Systems modelling of mitochondrial dynamics in different exercise regimes.
    Ali Khalilimeybodi, Lingxia Qiao, Allen Leung, Andrew D McCulloch, Simon Schenk, Padmini Rangamani.
      Exercise stimulates skeletal muscle signalling and mitochondrial metabolism. Emerging evidence shows that mitochondrial dynamics (i.e. fission and fusion) could be regulated by exercise. Yet, key gaps remain in identifying (i) the signals that drive fission vs. fusion; (ii) how energy status and reactive oxygen species (ROS) shift control between dynamin-related protein 1 (DRP1) and mitofusin (MFN)/optic atrophy 1 (OPA1); and (iii) which intensity-duration combinations yield similar cytosolic signals but different mitochondrial remodelling. Therefore, we developed an integrative computational framework connecting exercise regimens to mitochondria fission-fusion machinery by linking blood-myofibre energetics in cytosol and mitochondria to signalling pathways. The influence of sprint, resistance and endurance exercise regimens on mitochondrial fission and fusion has been simulated. Classified qualitative validation of the signalling network model achieved 80% accuracy. The model predicts regimen-specific dynamics starting with an acute DRP1-driven fission during exercise followed by MFN1/2-OPA1-mediated re-fusion as energy stress declines, consistent with a cyclical triage-then-rebuild paradigm. Changes are most pronounced and sustained with endurance, sharp but brief with sprint, and minimal with resistance. Global sensitivity analysis identified AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α→MFN1/2 as dominant fusion drivers, ROS and AMPK→mitochondrial fission factor/DRP1 as primary fission switches, and Ca2 +-calmodulin, extracellular-signal-regulated kinase and liver kinase B1/AMPK as shared regulators. The model predicts that an endurance base, augmented with one or two weekly high intensity interval training/sprint interval training sessions could maximize AMPK-ROS pulses and mitochondrial fission-fusion. This framework unifies muscle's signalling logic with energetic state to explain how intensity-volume combinations, bout spacing and kinase modulation tune mitochondrial remodelling, yielding testable predictions for optimizing training and adjuvant therapies to enhance mitochondrial quality and performance. KEY POINTS: Different exercise regimes such as sprint, resistance, and endurance can trigger different signalling pathways. Exercise also triggers mitochondrial remodelling in skeletal muscle. Using a systems biology model, we developed a systems biology model for skeletal muscle signalling and mitochondrial metabolism for exercise. Our model predicts the dynamics of mitochondrial fusion and fission in different exercise regimes and identifies which signalling pathways dominassste these remodelling mechanisms.
    Keywords:  ROS‐mediated signalling; exercise regime; metabolic signalling; mitochondrial fission; mitochondrial fusion
    DOI:  https://doi.org/10.1113/JP290424
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