bims-ripira Biomed News
on RRM2B MDMD in Adults
Issue of 2026–02–22
twelve papers selected by
Martín Lopo
  1. N-Acetylglucosamine Selectively Attenuates Neuroinflammation in a Mouse Model of Mitochondrial Dysfunction.
  2. Extracellular Vesicle-Derived Mitochondrial Genes as Potential Biomarkers for Brain Aging in Human.
  3. Unraveling riboflavin-mediated mitochondrial modulation as a therapeutic pathway in neurological disorders: an integrative systematic review.
  4. Hydrogel-based mitochondrial therapies: A new frontier in disease treatment.
  5. Curcumin Rescues Oxidative Stress-Induced Impairment of PINK1/Parkin Pathway-Mediated Mitophagy in APOE4-Expressing Astrocytes.
  6. Mitochondria: the central hub linking exercise to enhanced cardiac function.
  7. Characterizing mitochondrial phenotypes and MERCS in aged human skeletal muscle myoblasts.
  8. Mitochondrial Metabolism in Neutrophils: Emerging Roles in Inflammatory Skin Diseases.
  9. Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.
  10. CypD Dependent mPTP Opening Is Crucial for Oxidized Mitochondrial DNA Release in Ferroptosis.
  11. Redox therapy for neuropsychiatric disorders: Molecular mechanisms and biomarker development.
  12. Brain fatigue in Graves' disease - symptoms and presentation of a possible mechanism at the cellular level.
  1. Acta Physiol (Oxf). 2026 Mar;242(3): e70179
    N-Acetylglucosamine Selectively Attenuates Neuroinflammation in a Mouse Model of Mitochondrial Dysfunction.
    Laura Jiménez-Sánchez, Paula Ruiz-López, Pilar González-García, Janne Purhonen, Juan Manuel Martínez-Gálvez, Sergio López-Herrador, Julia Corral-Sarasa, María Elena Díaz-Casado, Carmen Venegas, Isaac Santos-Pérez, Enrica Olivieri, Adriana L Rojas, Luis Carlos López.
       AIM: Mitochondrial dysfunction plays a central role in multiple neurodegenerative diseases, yet the temporal sequence of cellular events underlying neurodegeneration remains poorly defined. This study aimed to characterize the progression of neurodegeneration in a mouse model of fatal mitochondrial encephalopathy and to evaluate the therapeutic potential of oral N-acetylglucosamine supplementation.
    METHODS: A mouse model of primary coenzyme Q deficiency was used to examine neurodegeneration at presymptomatic, symptomatic and terminal stages. Neuronal integrity, glial activation, myelination and inflammatory responses were assessed using histological, molecular and ultrastructural approaches, together with behavioral analysis of motor coordination. N acetylglucosamine was administered orally from 1 month of age, and its effects on neuroinflammation, myelin integrity and motor performance were evaluated.
    RESULTS: Astrocyte activation and neuronal loss were detected before the onset of clinical symptoms, whereas proinflammatory microglia appeared at later disease stages. Early myelin abnormalities were accompanied by an initial increase in oligodendrocyte precursor cells, suggesting a compensatory response to early myelin stress. Oral N-acetylglucosamine supplementation reduced glial activation and neuroinflammatory markers, likely through modulation of inflammatory signaling pathways. Although treatment did not fully reverse structural damage or restore myelin protein expression, it led to a significant improvement in motor coordination.
    CONCLUSION: These findings define a temporal sequence of early glial activation, neuronal loss, and myelin alterations in mitochondrial encephalopathy. Targeting glial responses and neuroinflammation at early disease stages may mitigate neurodegenerative progression and improve functional outcomes, highlighting a physiologically relevant therapeutic window for mitochondrial disorders.
    Keywords:  N‐acetylglucosamine; coenzyme Q; mitochondria; neuroinflammation
    DOI:  https://doi.org/10.1111/apha.70179
  2. J Gerontol A Biol Sci Med Sci. 2026 Feb 17. pii: glag044. [Epub ahead of print]
    Extracellular Vesicle-Derived Mitochondrial Genes as Potential Biomarkers for Brain Aging in Human.
    Qian Yu, Shuyi Yu, Hang Chen, Zhikang Cui, Qian Cheng, Yan Jin, Shuai Zong, Yunshan Wang, Ming Li, Zhiming Lu.
      Aging significantly impacts brain function, and identifying reliable biomarkers for early detection of age-related neurodegeneration is crucial for improving diagnosis and treatment outcomes. This proof-of-principle study aims to evaluate the abundance of mitochondrial DNA (mtDNA) targets within plasma-derived extracellular vesicles (EVs) and to investigate whether they correlate with established biomarkers of brain aging, independent of chronological age and renal function. mtDNA copy number was quantified using absolute quantitative PCR (qPCR). Brain aging biomarkers were measured by ELISA. Multivariable regression analysis was performed to examine the associations between EVs mitochondrial genes and aging biomarkers. A multi-biomarker model was developed to assess the performance of combined biomarkers in distinguishing between age groups. We observed that EV mitochondrial gene levels were significantly increased with age (P < 0.001). Levels of neurofilament light chain (NfL), amyloid-beta (Aβ42 and Aβ40), also showed significant age-related increases (P < 0.001). A multi-biomarker model combining EVs mitochondrial genes and brain aging biomarkers showed the optimal performance in distinguishing older adults from younger individuals, with an area under the ROC curve (AUC) significantly higher than that of any single biomarker (P < 0.01). These findings collectively indicate that EV-derived mitochondrial genes, in combination with other biomarkers like NfL, hold great potential as a non-invasive tool for early detection and monitoring of brain aging and neurodegenerative diseases.
    Keywords:  Aging; Biomarker; Extracellular vesicles; Mitochondrial Genes
    DOI:  https://doi.org/10.1093/gerona/glag044
  3. J Nutr. 2026 Feb 18. pii: S0022-3166(26)00076-3. [Epub ahead of print] 101427
    Unraveling riboflavin-mediated mitochondrial modulation as a therapeutic pathway in neurological disorders: an integrative systematic review.
    Eulália Rebeca Silva-Araújo, Ana Elisa Toscano, Henrique José Cavalcanti Bezerra Gouveia, Paula Brielle Pontes, Joaci Pereira Dos Santos Júnior, Osmar Henrique Dos Santos-Júnior, Maria Daniele Teixeira Beltrão de Lemos, Nathalia Caroline de Oliveira Melo, Janaina Viana de Melo, Eduardo Padrón-Hernández, Raul Manhães-de-Castro.
       BACKGROUND: Mitochondrial dysfunction is recognized as a key pathophysiological mechanism in neurodegenerative diseases. Alterations in mitochondrial dynamics-including imbalances in fission and fusion, impaired biogenesis, and disrupted mitophagy-contribute to the onset and progression of neurological disorders. In this context, mitochondrial modulation has emerged as a promising therapeutic strategy.
    OBJECTIVE: This systematic review examined the role of riboflavin, a water-soluble vitamin and essential mitochondrial cofactor, in neurological interventions through mitochondrial modulation, with emphasis on elucidating the underlying molecular mechanisms.
    METHODS: A search of the PubMed, Embase, Scopus, and Web of Science databases identified 23 eligible studies, comprising 6 in vitro experiments, 10 rodent models, and 7 clinical trials.
    RESULTS: These studies evaluated the effects of riboflavin in monogenic, neurodegenerative, and demyelinating mitochondrial diseases, cerebrovascular/hypoxic injury, and pain/migraine. Clinical evidence indicated that riboflavin may regulate oxidative stress in stroke and perinatal asphyxia, with associated functional improvements. Preclinical findings revealed mechanisms of action involving energy homeostasis, cell cycle regulation, and mitochondrial dynamics across monogenic mitochondrial disorders, neurodegenerative diseases, hypoxic injury, and models of pain and migraine. Possibly through mitochondrial modulation, riboflavin appeared to reduce α-synuclein aggregation in Parkinson's disease, increase the number of tyrosine-hydroxylase-positive neurons in Alzheimer's disease models, enhance neuronal survival in Brown-Vialetto-Van Laere and Huntington's disease models, and normalize neuronal excitability in ataxia and migraine. In contrast, no therapeutic effects were observed in demyelinating diseases.
    CONCLUSIONS: Overall, the findings suggest that riboflavin may promote neuroprotection through redox modulation and gene regulation, stabilization of membrane potential, and enhanced mitochondrial complex activity via flavin cofactors, ultimately supporting neuronal metabolism and functional outcomes. Despite advances in mechanistic understanding, clinical applications in humans remain insufficiently defined for most conditions, with clearer dosage regimens currently established only for stroke and migraine.
    Keywords:  brain; degenerative diseases; mitochondria; mitochondrial biogenesis; vitamin B2
    DOI:  https://doi.org/10.1016/j.tjnut.2026.101427
  4. Biomaterials. 2026 Feb 11. pii: S0142-9612(26)00095-5. [Epub ahead of print]330 124071
    Hydrogel-based mitochondrial therapies: A new frontier in disease treatment.
    Zihua Tang, Yu Jiang, Huiling Ling, Yifei Shen, Xingbo Wu, Chun Hung Chu, Irene Shuping Zhao, Xueqi Gan.
      Mitochondria are essential for cell energy metabolism, redox homeostasis, and apoptosis. Meanwhile, numerous pathological conditions are linked with mitochondrial dysfunction, such as cardiovascular diseases, connective tissue disorders, chronic wounds, neurological disorders, and cancer. Mitochondria-targeted hydrogels (MTHs) have emerged for their ability to selectively deliver active agents to mitochondria, modulate mitochondrial function precisely, which plays a key role in improving treatment efficacy. Hydrogels offer unique advantages, including biocompatibility, structural tunability, and controlled drug release. With specific targeting ligands and stimuli-responsive mechanisms, hydrogels can achieve mitochondrial localization and therapeutic modulation. Recent advancements have demonstrated significant benefits of MTHs in reducing oxidative stress, promoting oxidative phosphorylation and restoring mitochondrial quality control across a variety of disease models. However, challenges remain, including optimizing targeting efficiency, as well as accuracy. Further exploration of therapeutic mechanisms and the integration of multi-dimensional targeting strategies are also essential for the clinical application of MTHs. The current review highlights the development of mitochondrial targeting strategies and specifically focuses on a series of applications of MTHs in mitochondrial-related diseases. Lastly, the discussion delves into the shortcomings of existing therapies and possible future research ideas.
    Keywords:  Hydrogel engineering; Mitochondria-related diseases; Mitochondria-targeted hydrogels; Mitochondrial quality control; Tissue regeneration
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124071
  5. Mol Neurobiol. 2026 Feb 18. 63(1): 454
    Curcumin Rescues Oxidative Stress-Induced Impairment of PINK1/Parkin Pathway-Mediated Mitophagy in APOE4-Expressing Astrocytes.
    Jia-Xin Yu, Wen-Xuan Zhang, Pu-Yu Li, Yi-Liang Yang, Han-Chang Huang.
      Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by deterioration in memory, cognition, and learning ability. Its etiology is complex and influenced by multiple factors, including genetics and environment. With advancing research into mitochondrial function and mechanisms, impaired mitophagy has been proposed as a significant mechanism contributing to AD. The ApoE ε4 allele, a high-risk genetic factor for AD, may play a key role in disease pathogenesis by inducing mitophagy dysfunction and apoptosis. From the perspective of APOE gene polymorphisms, this study investigates abnormal changes in mitochondrial function and autophagy in humanized APOE4 mice primary astrocytes under oxidative stress, as well as the regulatory effect of curcumin (Cur) on mitophagy and oxidative stress-induced apoptosis, thereby exploring its potential to ameliorate AD through targeting mitophagy. Mitochondrial function analysis revealed that APOE4 expression reduced the antioxidant capacity and respiratory function of primary astrocytes, leading to mitochondrial membrane damage, intracellular reactive oxygen species (ROS) accumulation, and decreased ATP production. Curcumin effectively protected mitochondrial integrity, reduced the number of damaged mitochondria, improved overall mitochondrial function, and helped maintain mitochondrial homeostasis involving in PINK1/Parkin pathway. Regarding autophagy and apoptosis, curcumin was shown to restore autophagic flux, mitigate autophagy disruption caused by oxidative stress, and reverse early-stage apoptosis.
    Keywords:  APOE4; Astrocytes; Curcumin; Mitochondrial function; Mitophagy; Oxidative stress
    DOI:  https://doi.org/10.1007/s12035-026-05744-9
  6. Front Physiol. 2026 ;17 1747133
    Mitochondria: the central hub linking exercise to enhanced cardiac function.
    Jiaqin Cai, Tutu Wang, Shunchang Li.
      Sedentary lifestyle is a major risk factor for the occurrence and development of cardiovascular disease, which remains one of the leading contributors to global morbidity and mortality. Beyond inducing endothelial dysfunction, prolonged sedentary patterns trigger chronic inflammation and disrupt endogenous antioxidant defenses, resulting in mitochondrial dysfunction in cardiomyocytes and subsequent impairment of cardiac health. In contrast, regular physical exercise serves as an effective lifestyle intervention that mitigates sedentary-related cardiac damage and improves cardiac function. Mitochondria, as central organelles governing cellular survival and death, are thought to play a pivotal role in mediating the cardioprotective effects of exercise. However, the precise mitochondrial mechanisms underlying these benefits remain incompletely defined. This review aims to summarize current evidence on how exercise regulates mitochondrial function in the heart, with particular emphasis on recent advances linking mitochondrial respiration, dynamics, calcium homeostasis, inflammatory signaling, and oxidative stress to cardiac health. We further propose that exercise-induced improvements in mitochondrial function constitute a core mechanism underlying its cardioprotective effects. By comparing mitochondrial alterations under sedentary and exercise conditions, we provide a clearer mechanistic perspective on how lifestyle behaviors shape cardiac health. Furthermore, this paper also discusses signaling pathways that position mitochondria as key targets of exercise-induced cardiac protection.
    Keywords:  exercise; heart; inflammatory response; mitochondria; oxidative stress
    DOI:  https://doi.org/10.3389/fphys.2026.1747133
  7. PLoS One. 2026 ;21(2): e0343604
    Characterizing mitochondrial phenotypes and MERCS in aged human skeletal muscle myoblasts.
    Yufu Unten, Kazuaki Takafuji, Yumiko Masukagami, Isshin Shiiba, Keigo Horiuchi, Filip Husnik, Shigeru Yanagi, Norifumi Tateishi, Toshihide Suzuki.
      Age-associated declines in skeletal muscle function are linked to cellular senescence and mitochondrial alterations, yet mitochondrial phenotypes in aged human myoblasts remain insufficiently characterized. Here, we examined primary skeletal muscle myoblasts from young and elderly donors to assess mitochondrial function, morphology, and mitochondria-endoplasmic reticulum (ER) contact sites (MERCS). Myoblasts from older donors exhibited senescence features, including elevated SA-β-gal activity and reduced Lamin B1 expression, accompanied by increased mitochondrial oxidative stress. Despite marked mitochondrial hyperfusion and increased mitochondrial DNA content, mitochondrial oxygen consumption rate and membrane potential per mitochondrial area were comparable between young and old cells. MERCS were significantly elevated in aged myoblasts and were reduced by scavenging mitochondrial reactive oxygen species (mtROS), indicating an association between oxidative stress and MERCS formation. These findings suggest that mitochondrial hyperfusion and enhanced MERCS accompany cellular aging in human myoblasts and may contribute to maintaining mitochondrial function under elevated oxidative stress.
    DOI:  https://doi.org/10.1371/journal.pone.0343604
  8. Br J Dermatol. 2026 Feb 18. pii: ljag060. [Epub ahead of print]
    Mitochondrial Metabolism in Neutrophils: Emerging Roles in Inflammatory Skin Diseases.
    Fangru Zhao, Yaoxing Guo, Yingdi Jiao, Wanting Zou, Yushuo Liu, Wanyu Li, Lingjie Gao, Wenyu Wan, Rui-Qun Qi.
      Neutrophils, the most abundant of the circulating leucocytes, play crucial roles in antimicrobial defence, tissue remodelling, and immune regulation. Traditionally regarded as predominantly glycolytic, relying on aerobic glycolysis (the Warburg effect) for rapid ATP generation, neutrophils are now recognised to possess broader metabolic flexibility. Emerging evidence has revealed their capacity for oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and glutaminolysis. As a result, mitochondrial metabolism is dynamically reprogrammed during differentiation and activation. These metabolic shifts in mitochondria profoundly influence essential neutrophil functions, including extracellular trap (NET) formation, reactive oxygen species (ROS) generation, chemotaxis, and apoptosis. In inflammatory skin diseases, mitochondrial dysfunction amplifies pathological responses by enhancing ROS production and driving NETosis. Specifically, in conditions such as psoriasis, cutaneous lupus erythematosus, and Behçet's disease, neutrophil mitochondrial activity is markedly increased, and this increase correlates with disease activity and progression. Notably, mitochondrial ROS have emerged as critical mediators of inflammation, triggering pathways such as PAD4 (peptidylarginine deiminase type 4)-dependent NETosis, inflammasome activation, and proinflammatory cytokine release. Accordingly, therapeutic strategies targeting neutrophil mitochondrial pathways, including ROS scavengers, mitophagy inducers, and metabolic modulators, are gaining increasing attention as promising approaches to mitigate neutrophil-driven skin inflammation. In this review recent advances in understanding mitochondrial metabolism in neutrophils, with particular emphasis on the pathological roles and therapeutic potential of this metabolism as related to inflammatory skin disorders are described.
    DOI:  https://doi.org/10.1093/bjd/ljag060
  9. Mol Genet Metab Rep. 2026 Mar;46 101296
    Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.
    Wiebke Hahn, Karla Erffmeier, Maximilian Schulze, Felix Zahnert, Susanne Knake, Panagiota-Eleni Tsalouchidou.
       Background: Mutations in COQ8A cause primary coenzyme Q10 deficiency, which can present clinically heterogeneously: Symptoms range from cerebellar ataxia, epilepsy, encephalomyopathy, macular degeneration to nephropathy. High-dose coenzyme Q10 supplementation is widely used, yet there is little evidence on complementary strategies, particularly for non-epileptic features such as cerebellar ataxia.
    Case presentation: We report a 46-year-old female with genetically confirmed COQ8A-related coenzyme Q10 (CoQ10) deficiency, presenting with ataxia and epilepsy characterized by myoclonic and bilateral tonic-clonic seizures, who participated in a clinical protocol of ketogenic intermittent fasting, a method of intermittent fasting combined with medium-chain triglycerides (MCT) primarily designed for seizure management. The patient followed a 16:8 intermittent fasting regime combined with MCT intake for three months, followed by three months of all-alone intermittent fasting. Routine blood markers and brain MRI, including diffusion imaging were obtained before and after ketogenic fasting.
    Results: During the study protocol, while no seizure reduction in myoclonic seizures could be observed, ataxia - quantified by the Scale for the Assessment and Rating of Ataxia (SARA) - improved significantly from 8.5 to 6.0 during the interventions. MRI showed a trend suggesting improved cerebellar microstructural integrity.
    Conclusions: This case highlights the potential of ketogenic intermittent fasting as an adjunct therapy for mitochondrial ataxia. Ketogenic intermittent fasting was associated with clinically meaningful improvement of ataxia in a patient with COQ8A-related CoQ10 deficiency, suggesting that ketogenic dietary strategies may represent a promising adjunct therapeutic approach for mitochondrial ataxia. Future research should assess this intervention in larger patient cohorts to confirm its potential benefits.
    Keywords:  Ataxia; Coenzyme Q10 deficiency; IF-MCT study; Intermittent fasting; Ketogenic diet; Mitochondrial diseasse
    DOI:  https://doi.org/10.1016/j.ymgmr.2026.101296
  10. Adv Sci (Weinh). 2026 Feb 17. e02239
    CypD Dependent mPTP Opening Is Crucial for Oxidized Mitochondrial DNA Release in Ferroptosis.
    Hong Zhou, Wan Fu, Shizuo Liu, Zili Zhang, Hanyan Luo, Qing Zhong.
      Ferroptosis is a type of regulated cell death characterized by the accumulation of lipid peroxides that damage cell membranes specifically. Mitochondrial swelling and dysfunction are hallmarks of ferroptosis; however, what causes mitochondrial swelling and the consequences of mitochondrial swelling in ferroptotic signal transduction remain poorly understood. Our study found that mitochondrial permeability transition pore (mPTP) opening is essential for mitochondrial swelling and ferroptosis activation. During ferroptosis, oxidized mitochondrial DNAs (mtDNAs) are released through the mPTP. These oxidized mtDNAs activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, promoting ferroptosis through activating ferrotinophagy. Consistently, inhibition of mtDNA-repair enhances cellular sensitivity to ferroptosis and therefore synergizes with ferroptosis inducer in suppressing tumorigenesis in mouse xenograft tumor models. This study provides a fundamental understanding of how mPTP engages in ferroptosis by releasing mitochondrial DNAs as crucial messengers to activate ferroptotic signaling.
    Keywords:  cGAS‐STING; ferroptosis; mPTP; mitochondria; mtDNA
    DOI:  https://doi.org/10.1002/advs.202502239
  11. Sci Adv. 2026 Feb 20. 12(8): eaea9014
    Redox therapy for neuropsychiatric disorders: Molecular mechanisms and biomarker development.
    Kyle W Cuklanz, Abigail Stein, Virginie-Anne Chouinard, Dost Ongur, Fei Du.
      Redox dysregulation, characterized by an imbalance in the NAD+ [nicotinamide adenine dinucleotide (oxidized form)]/NADH (reduced form of NAD+) ratio, is implicated in neurodegenerative and psychiatric disorders such as Alzheimer's disease and schizophrenia. This imbalance contributes to mitochondrial dysregulation, oxidative stress, and inflammation. Despite promising preclinical studies supporting therapeutic strategies aimed at restoring redox balance and thereby rescuing brain bioenergetic deficits, clinical outcomes and efficacy remain limited. Progress has been hindered by the incomplete understanding of NAD+ subcellular cycling, as well as a lack of in vivo biomarkers measuring target engagement of redox status and mitochondrial function. Thus, this review examines molecular mechanisms of NAD (nicotinamide adenine dinucleotide)-related bioenergetic deficits, current and emerging NAD-targeted therapies, and recent advances in the development of neuroimaging biomarkers, emphasizing personalized and mechanism-driven approaches.
    DOI:  https://doi.org/10.1126/sciadv.aea9014
  12. Eur Thyroid J. 2026 Feb 19. pii: ETJ-25-0172. [Epub ahead of print]
    Brain fatigue in Graves' disease - symptoms and presentation of a possible mechanism at the cellular level.
    Karin Tammelin, Mats Holmberg, Agneta Lindo, Birgitta Johansson, Lars Rönnbäck, Helena Filipsson Nyström.
      Fatigue in patients with Graves' disease (GD) is characterized by a profound lack of mental energy that affects daily functioning, including work. This symptom is particularly prominent in the early stages of the disease, affecting more than 50% of patients, but in some cases, it persists even after successful endocrinological treatment and restoration of euthyroidism. Individuals with persistent fatigue often seek support. Because this tiredness originates in the brain, we refer to it as brain fatigue. It is accompanied by a cluster of interconnected symptoms as cognitive, sensory, and emotional, which we define collectively as brain fatigue syndrome (BFS). BFS is marked by reduced perceived energy levels and associated impairments across multiple domains. The aim of this paper is to improve understanding and identification of BFS in GD, and to propose potential treatment options. We also propose a hypothesis, supported by robust preclinical evidence, that the inflammatory response in this autoimmune disorder may lead to astrocyte dysfunction, impairing neuronal signalling for multiple neurotransmitters. This could reduce the efficiency of brain information processing, increase activation of larger brain areas, and diminish glucose uptake from the bloodstream. Such changes may result in widespread brain dysfunction, culminating in an energy crisis that manifests as profound fatigue and cognitive, sensory, and emotional impairments. However, this hypothesis needs to be tested in humans, particularly regarding the persistence of brain fatigue in GD after normalisation of thyroid hormone levels.
    Keywords:  CNS inflammation; Graves’ disease; astrocyte; autoimmunity; brain fatigue syndrome; fatigue
    DOI:  https://doi.org/10.1530/ETJ-25-0172
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