bims-ripira Biomed News
on RRM2B MDMD in Adults
Issue of 2026–02–01
sixteen papers selected by
Martín Lopo
  1. Mitochondrial DNA: A Key Alarmin Igniting the Inflammasome Fire in Health and Disease.
  2. Mito-nuclear communication: From cellular responses to organismal health.
  3. Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson's disease model by improving mitochondrial function.
  4. [Super-refractory status epilepticus caused by hereditary mitochondrial disease].
  5. Mitochondrial responses to thermal stress: ROS dynamics and metabolic shifts in Drosophila.
  6. Diagnosis and Management of Heat-related Illness: Clinical and Molecular Perspectives.
  7. Associations between the brain glymphatic system and mitochondrial (dys)function: a systematic review.
  8. Bioactive Peptide C248 of PRDX4 Ameliorates the Function of Testicular Leydig Cells via Mitochondrial Protection.
  9. Mitochondrial dysfunction-induced PANoptosis: Mechanisms, triggers, and disease implications.
  10. Lactylation in post-stroke fatigue: linking metabolic dysregulation to neuroinflammation.
  11. Mitochondria and Aging: Redox Balance Modulation as a New Approach to the Development of Innovative Geroprotectors (Fundamental and Applied Aspects).
  12. Mitochondrial Dysfunction: The Cellular Bridge from Emotional Stress to Disease Onset: A Narrative Review.
  13. Mitochondrial DNA Instability and Neuroinflammation: Connecting the Dots Between Base Excision Repair and Neurodegenerative Disease.
  14. Serum cell-free mitochondrial DNA under a highly standardized and controlled stress induction.
  15. Coenzyme Q10 supplementation raises plasma levels without improving mitochondrial function in older adults.
  16. Hereditary Polyneuropathies in the Era of Precision Medicine: Genetic Complexity and Emerging Strategies.
  1. Immunology. 2026 Jan 29.
    Mitochondrial DNA: A Key Alarmin Igniting the Inflammasome Fire in Health and Disease.
    Woo Hyun Park.
      Beyond their classical role as cellular powerhouses, mitochondria are now recognised as indispensable hubs for innate immune signalling. A pivotal aspect of this function is the release of mitochondrial DNA (mtDNA), a potent damage-associated molecular pattern (DAMP) that, when misplaced, acts as a powerful alarmin due to its prokaryotic origins. In response to cellular stress or infection, mtDNA translocates to the cytosol and activates intracellular protein platforms known as inflammasomes, triggering the maturation of cytokines like interleukin-1β (IL-1β) and inducing a lytic form of cell death, pyroptosis. This review synthesises current research on this intricate relationship. Whilst potassium (K+) efflux remains the canonical trigger for the NLR family pyrin domain containing 3 (NLRP3) inflammasome, emerging and debated roles of oxidised mtDNA (ox-mtDNA) as a potential direct ligand or critical upstream amplifier are explored. The manuscript elucidates mtDNA release mechanisms, such as mitochondrial permeability transition pore (mPTP) opening, and explores the role of amplifying pathways like the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis and cytidine/uridine monophosphate kinase 2 (CMPK2)-mediated mtDNA synthesis. The profound involvement of the mtDNA-inflammasome axis is surveyed across a spectrum of pathologies, including autoimmune, metabolic, neurodegenerative, and cardiovascular diseases. The compiled evidence establishes mtDNA as a universal trigger of inflammation and a unifying pathogenic driver across this diverse disease landscape, highlighting the significant therapeutic potential of modulating this fundamental immune signalling axis to treat a multitude of human diseases.
    Keywords:  immunogenic cell death; inflammasome; innate immunity; mitochondrial DNA; pyroptosis; sterile inflammation
    DOI:  https://doi.org/10.1111/imm.70111
  2. Mol Cell. 2026 Jan 28. pii: S1097-2765(26)00021-3. [Epub ahead of print]
    Mito-nuclear communication: From cellular responses to organismal health.
    Guanyu Chen, Hangyu Dong, Ye Tian.
      The co-evolution of mitochondria and the nucleus established constant mito-nuclear communication that is essential for both cellular and organismal homeostasis. At the cell-autonomous level, mitochondrial perturbations activate retrograde pathways such as the mitochondrial unfolded protein response (UPRmt) and the mitochondrial integrated stress response (ISRmt), which couple organelle dysfunction to nuclear transcriptional programs, thereby promoting mitochondrial function and preserving cellular integrity. Importantly, this communication is not confined to individual cells but extends across tissues to coordinate systemic adaptations. Stress signals can be sensed, broadcasted through secreted mitokines and neural circuits, and then interpreted by distal organs to coordinate systemic adaptations. These systemic responses integrate metabolism, immunity, and behavior, conferring resilience to stress and shaping the trajectory of aging. Understanding this multi-layered communication, from the organelle to the organism and its microbial ecosystem, promises new therapeutic strategies to enhance mitochondrial function, promote resilience, and extend healthspan.
    Keywords:  ISRmt; UPRmt; aging; mito-nuclear communication; mitokine; proteostasis
    DOI:  https://doi.org/10.1016/j.molcel.2026.01.001
  3. Mitochondrion. 2026 Jan 26. pii: S1567-7249(26)00001-2. [Epub ahead of print]87 102111
    Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson's disease model by improving mitochondrial function.
    Yu Si, Muhammad Abid Hayat, Yingyin Ni, Jingwen Zhang, Tao Guo, Yudie Cao, Yancheng Hong, Hao Zuo, Xin Sun, Zheng Li, Bo Chen, Jia Wan, Yong Wang, Jiabo Hu.
      Parkinson's disease (PD) is the second most common neurodegenerative disorder related to mitochondrial dysfunction. Recent studies have reported that mitochondrial transfer between cells occurred naturally and was effective for alleviating mitochondrial dysfunction. In the current study, functional exogenous mitochondria (Mito) were extracted and administered to both in vitro and in vivo PD models, exploring the therapeutic effects of Mito on damaged neurons. It was observed that in the in vitro PD model, Mito improved cell morphology and increased cell viability from 25.06% to 42.44% (p < 0.001), while enhancing mitochondrial activity within the cells by a 201% increase in the JC-1 red/green fluorescence ratio (p = 0.02). Further analysis suggests that Mito's neuroprotective effects are potentially mediated via integrated modulation of neuroinflammation and ferroptosis pathways. The findings of the in vivo PD model showed that Mito improved motor coordination in the rotational test by 71% (p < 0.01) and ameliorated depression-like behavior demonstrating a 13.4% enhancement in Sucrose preference (p < 0.001), accompanied by histological evidence of neuroprotection observed in Nissl-stained brain sections and the significant recovery in mitochondrial function by 31.6% (p = 0.01). This study is the first to demonstrate that Mito can enter a PD cell model and rescue neuronal and mitochondrial damage in both in vivo and in vitro settings, with transcriptomic analysis revealing the involvement of key molecular pathways related to neuroinflammation and ferroptosis. This offers new insights and prospectus therapeutic strategies for PD as well as a foundation for future research in clinical medicine.
    Keywords:  Mitochondria; Mitochondrial transplantation; Neurodegenerative diseases; Neurons; Parkinson’sdisease
    DOI:  https://doi.org/10.1016/j.mito.2026.102111
  4. Ugeskr Laeger. 2026 Jan 26. pii: V07250609. [Epub ahead of print]188(5):
    [Super-refractory status epilepticus caused by hereditary mitochondrial disease].
    Niels Bach Sørensen, Kristina Stamenkovic, Ellen Hollands Steffensen, Inge Ring Kofoed.
      In this case report, we present an 11-year-old girl who developed super-refractory status epilepticus (SRSE) after focal seizures. Initial investigations, including MRI, CSF analysis, and autoimmune panels, were normal. Despite extensive treatment with several anti-seizure medications, immunotherapy, attempt of treatment with ketogenic diet and anesthetic infusions targeting burst-suppression, no improvement occurred. Trio whole genome sequencing revealed compound heterozygous pathogenic variants in POLG, confirming mitochondrial disease. Due to poor prognosis and deterioration, treatment was withdrawn, and she died in ICU.
    DOI:  https://doi.org/10.61409/V07250609
  5. Mitochondrion. 2026 Jan 25. pii: S1567-7249(26)00004-8. [Epub ahead of print] 102114
    Mitochondrial responses to thermal stress: ROS dynamics and metabolic shifts in Drosophila.
    Adèle Léger, Léa Herpe, Nicolas Pichaud.
      Temperature critically impacts ectotherm metabolism, notably mitochondrial respiration, enzyme activity, and ATP production. However, the effect of temperature on reactive oxygen species (ROS) production remains poorly understood in these organisms. Here, we investigated the thermal sensitivity of H2O2 production by isolated mitochondria from Drosophila melanogaster. We measured H2O2 emission rates at six temperatures (18-45 °C) during: (i) oxidative phosphorylation (OXPHOS) fueled by NADH-linked substrates feeding electrons into complex I (CI), as well as by FADH2-linked substrates such as proline, succinate, and glycerol-3-phosphate (G3P); and (ii) during non-phosphorylating conditions with FADH2-linked substrates as well as using defined substrate/inhibitor combinations such as pyruvate, malate and rotenone (P/M-driven), as well as supported by proline, succinate, and G3P when inhibitors are present. We calculated relative H2O2 emission rates and compared them with previously measured enzyme activities and oxygen consumption rates. Our results show marked thermal sensitivity of H2O2 emission during OXPHOS and when P/M-driven. At elevated temperatures, increased ROS production by NADH-linked substrates during OXPHOS coincided with a decline in CI-induced oxygen consumption capacity and pyruvate dehydrogenase (PDH) activity, indicating a dysfunction in NADH-producing and -consuming systems. In contrast, substrates feeding electrons into the Q pool via FADH2 oxidation support respiration at high temperature decoupled from ROS production, suggesting a metabolic strategy to sustain respiration while limiting oxidative stress. These findings highlight that mitochondrial thermal sensitivity involves a complex regulation of ROS metabolism. Our study provides new insights into mitochondrial ROS dynamics and their implications for upper thermal tolerance in insects.
    Keywords:  Drosophila melanogaster; Enzymatic activities; Mitochondrial oxygen consumption; Reactive oxygen species; Thermal sensitivity
    DOI:  https://doi.org/10.1016/j.mito.2026.102114
  6. Juntendo Med J. 2025 ;71(6): 399-405
    Diagnosis and Management of Heat-related Illness: Clinical and Molecular Perspectives.
    Julie Helms, Kenta Kondo, Kunishiko Nagakari, Toshiaki Iba.
      Heat-related illness (HRI) represents a growing public health challenge in the context of global warming. Ranging from mild symptoms such as heat cramps to life-threatening heatstroke, HRI requires prompt recognition and appropriate management to reduce morbidity and mortality. The diagnosis of HRI is primarily based on clinical symptoms but is supported by laboratory evaluation, especially in severe cases. Heatstroke, the most critical form, is defined by core body temperature ≥ 40°C and central nervous system dysfunction. In addition to conventional laboratory markers, recent advances in molecular biology have identified several biomarkers, such as heat shock proteins, HMGB1 (High Mobility Group Box 1), and mitochondrial DNA, which may improve early and accurate detection and prognostication. This review summarizes the diagnostic approach to HRI, highlighting key clinical findings, laboratory assessments, and emerging molecular markers.
    Keywords:  cell death; damage-associated molecular patterns; heat stroke; leukocyte; mitochondria; organ dysfunction
    DOI:  https://doi.org/10.14789/ejmj.JMJ25-0024-R
  7. Front Neurosci. 2025 ;19 1726054
    Associations between the brain glymphatic system and mitochondrial (dys)function: a systematic review.
    Tilda Pihala, Vesa Kiviniemi, Mika H Martikainen.
       Introduction: Previous studies have shown that the proper functioning of both mitochondria and the glymphatic system transporting metabolites are essential for brain health. The aim of this systematic review was to identify the current evidence-based data regarding the relationship between mitochondria and the glymphatic system.
    Methods: This systematic review was conducted following PRISMA guidelines. The databases of PubMed, Scopus, Medline, and Web of Science were searched on June 11, 2024, for eligible studies published until June 1, 2024.
    Results: Of 103 studies, six were included: two original studies and four review articles. All the included studies consistently indicated that the mitochondria and the glymphatic system are likely interconnected, with evidence suggesting several potential links between them. According to original studies, mitochondrial abnormalities in idiopathic normal pressure hydrocephalus (iNPH) and idiopathic intracranial hypertension (IIH) may disrupt glymphatic system function. The included reviews highlighted REM sleep deprivation, melatonin, and inflammation as potential factors linking mitochondria and the glymphatic system.
    Discussion: The relationship between mitochondria and the glymphatic system is complex. Further research is needed to clarify the precise mechanisms of interaction as the current literature is largely speculative. Existing evidence suggests that mitochondrial abnormalities are present in iNPH and IIH, conditions related to impaired CSF flow and impaired glymphatic function. In addition, sleep and melatonin potentially link mitochondrial activity and the glymphatic system function and thus offer potential avenues to ameliorate disorders associated with glymphatic dysfunction by enhancing mitochondrial activity.
    Keywords:  glymphatic system; idiopathic intracranial hypertension; idiopathic normal pressure hydrocephalus; melatonin; mitochondria; neurodegeneration
    DOI:  https://doi.org/10.3389/fnins.2025.1726054
  8. Antioxidants (Basel). 2025 Dec 22. pii: 21. [Epub ahead of print]15(1):
    Bioactive Peptide C248 of PRDX4 Ameliorates the Function of Testicular Leydig Cells via Mitochondrial Protection.
    Nini Wei, Shuning Yuan, Li Gao, Bei Zhang, Zhengjie Yan, Chao Gao, Yan Meng, Yugui Cui.
       BACKGROUND: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs' function.
    METHODS: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H2O2). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H2O2) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2'-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested.
    RESULTS: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01).
    CONCLUSION: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction.
    Keywords:  LCs senescence; antioxidant peptide; mitochondrial protection; nicotinamide mononucleotide; peroxiredoxin 4
    DOI:  https://doi.org/10.3390/antiox15010021
  9. Mitochondrion. 2026 Jan 25. pii: S1567-7249(26)00005-X. [Epub ahead of print] 102115
    Mitochondrial dysfunction-induced PANoptosis: Mechanisms, triggers, and disease implications.
    Liyang Pan, Shijie Fang, Fanhua Kong, Shaojun Ye, Yan Xiong.
      In recent years, PANoptosis, as a novel form of cell death that integrates multiple cell death pathways, has progressively emerged as a cutting-edge research field in the study of cell death and immune regulation. PANoptosis, a recently proposed form of inflammatory programmed cell death, integrates features of pyroptosis, apoptosis, and necroptosis, while emphasizing their interplay. It is mediated by the PANoptosome and plays a pivotal role in infections, inflammation, tumors, and degenerative diseases. Recent studies have demonstrated that ROS serve as critical signaling molecules for PANoptosome assembly. Given that mitochondria constitute the primary intracellular source of ROS, this establishes a crucial link between mitochondrial and PANoptosis activation. Mitochondria sustain energy production, calcium homeostasis, and signaling but also contribute to immune responses and cell death. Oxidative stress, obesity, and environmental pollutants can induce mitochondrial dysfunction, manifested through impaired mitochondrial dynamics, which subsequently leads to excessive ROS production and mtDNA leakage. These pathological changes ultimately trigger PANoptosis activation. This review systematically summarizes how mitochondrial dysfunction triggers PANoptosis through mechanisms such as ROS accumulation, aberrant mitochondrial dynamics, and mtDNA leakage. Furthermore, it explores the implications of this process in traumatic brain injury, inflammatory diseases, ischemic disorders, and diseases induced by environmental toxins (e.g., microplastics and heavy metals). Understanding the interplay between mitochondria and PANoptosis may provide critical insights into the pathogenesis of inflammation-related diseases and offer novel mitochondria-targeted therapeutic strategies.
    Keywords:  Mitochondrial DNA; Mitochondrial dynamics; Mitochondrial dysfunction; PANoptosis; PANoptosome; Reactive oxygen species
    DOI:  https://doi.org/10.1016/j.mito.2026.102115
  10. Front Neurosci. 2025 ;19 1713149
    Lactylation in post-stroke fatigue: linking metabolic dysregulation to neuroinflammation.
    Zekai Hu, Qingui Sun, Xinhao Liu, Jinyan Wang, Xieyun Jin, Jun Hu.
      Lactylation, a recently identified post-translational modification derived from lactate, has emerged as a key immunometabolic regulator in neurological disorders. In the context of ischemic stroke, abnormal lactate accumulation not only reflects energy metabolism dysfunction but also drives protein lactylation, which dynamically influences neuronal survival, glial activation, and neuroinflammatory cascades. Increasing evidence indicates that lactylation modulates transcriptional programs of microglia and astrocytes, amplifying inflammatory responses through histone modifications and metabolic enzyme regulation. These processes contribute critically to the onset and persistence of post-stroke fatigue (PSF), a debilitating complication that impairs recovery and quality of life in stroke survivors. This review integrates recent findings on lactylation-mediated regulation of immune and inflammatory pathways, with a particular focus on its effects on apoptosis-related signaling, mitochondrial dysfunction, and cytokine production. Furthermore, we highlight lactylation-related enzymes, including p300 and HDAC3, as potential therapeutic targets, and discuss emerging biomarkers for monitoring lactylation dynamics in stroke patients. By framing lactylation as a metabolic-epigenetic bridge connecting cellular energy states with immune responses, this article provides new insights into the immunopathogenesis of PSF and identifies promising directions for translational intervention.
    Keywords:  energy metabolism; inflammatory response; lactylation; neuronal apoptosis; post-stroke fatigue; protein post-translational modification
    DOI:  https://doi.org/10.3389/fnins.2025.1713149
  11. Int J Mol Sci. 2026 Jan 14. pii: 842. [Epub ahead of print]27(2):
    Mitochondria and Aging: Redox Balance Modulation as a New Approach to the Development of Innovative Geroprotectors (Fundamental and Applied Aspects).
    Ekaterina Mironova, Igor Kvetnoy, Sofya Balazovskaia, Viktor Antonov, Stanislav Poyarkov, Gianluigi Mazzoccoli.
      Redox (reduction-oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H2O2), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli-from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a "generator" of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization-from subcellular to systemic-are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms-from molecular and cellular to tissue, organ, and organismal levels-with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.
    Keywords:  aging; antioxidants; glutathione; mitochondria; oxidative stress; redox regulation
    DOI:  https://doi.org/10.3390/ijms27020842
  12. Biomolecules. 2026 Jan 08. pii: 117. [Epub ahead of print]16(1):
    Mitochondrial Dysfunction: The Cellular Bridge from Emotional Stress to Disease Onset: A Narrative Review.
    Sakthipriyan Venkatesan, Cristoforo Comi, Fabiola De Marchi, Teresa Esposito, Carla Gramaglia, Carlo Smirne, Mohammad Mostafa Ola Pour, Mario Pirisi, Rosanna Vaschetto, Patrizia Zeppegno, Elena Grossini.
      Severe emotional stress constitutes a significant public-health concern associated with negative health outcomes. Although the clinical effects are well acknowledged, the specific biological mechanisms that translate emotional suffering into systemic disease remain incompletely understood. Psychological stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, which directly target mitochondria and alter their bioenergetic and redox capacity. For this reason, this narrative review proposes that mitochondria serve as the primary subcellular link in the mind-body connection, as they play a pivotal role in converting neuroendocrine signals into cellular dysfunction. In particular, we focus on the concept of mitochondrial allostatic load (MALT), a framework explaining how the progressive decline in mitochondrial functions, from their initial adaptive roles in energy production, reactive oxygen species signaling, and calcium regulation, to being sources of inflammation and systemic damage, occurs when stress exceeds regulatory limits. We also, discuss how this transition turns mitochondria from adaptive responders into drivers of multi-organ disease. In subsequent sections, we examine diagnostic potentials related to MALT, including the use of biomarkers, such as growth differentiation factor 15, cell-free mitochondrial desoxyribonucleic acid, and functional respirometry. Furthermore, we evaluate mitochondria-targeted therapeutic strategies, encompassing pharmacological compounds, such as mitoquinone mesylate, Skulachev ions, and elamipretide, alongside lifestyle and psychological interventions. Here, we aim to translate MALT biology into clinical applications, positioning mitochondrial health as a target for preventing and treating stress-related disorders. We propose that MALT may serve as a quantifiable bridge between emotional stress and somatic disease, enabling future precision medicine strategies integrating mitochondrial care.
    Keywords:  allostatic load; mitochondrial dysfunction; psychosocial stress; reactive oxygen species; relationship trauma; systemic nervous system
    DOI:  https://doi.org/10.3390/biom16010117
  13. Genes (Basel). 2026 Jan 13. pii: 82. [Epub ahead of print]17(1):
    Mitochondrial DNA Instability and Neuroinflammation: Connecting the Dots Between Base Excision Repair and Neurodegenerative Disease.
    Magan N Pittman, Mary Beth Nelsen, Marlo K Thompson, Aishwarya Prakash.
      Neurons have exceptionally high energy demands, sustained by thousands to millions of mitochondria per cell. Each mitochondrion depends on the integrity of its mitochondrial DNA (mtDNA), which encodes essential electron transport chain (ETC) subunits required for oxidative phosphorylation (OXPHOS). The continuous, high-level ATP production by OXPHOS generates reactive oxygen species (ROS) that pose a significant threat to the nearby mtDNA. To counter these insults, neurons rely on base excision repair (BER), the principal mechanism for removing oxidative and other small, non-bulky base lesions in nuclear and mtDNA. BER involves a coordinated enzymatic pathway that excises damaged bases and restores DNA integrity, helping maintain mitochondrial genome stability, which is vital for neuronal bioenergetics and survival. When mitochondrial BER is impaired, mtDNA becomes unstable, leading to ETC dysfunction and a self-perpetuating cycle of bioenergetic failure, elevated ROS levels, and continued mtDNA damage. Damaged mtDNA fragments can escape into the cytosol or extracellular space, where they act as damage-associated molecular patterns (DAMPs) that activate innate immune pathways and inflammasome complexes. Chronic activation of these pathways drives sustained neuroinflammation, exacerbating mitochondrial dysfunction and neuronal loss, and functionally links genome instability to innate immune signaling in neurodegenerative diseases. This review summarizes recent advancements in understanding how BER preserves mitochondrial genome stability, affects neuronal health when dysfunctional, and contributes to damage-driven neuroinflammation and neurodegenerative disease progression. We also explore emerging therapeutic strategies to enhance mtDNA repair, optimize its mitochondrial environment, and modulate neuroimmune pathways to counteract neurodegeneration.
    Keywords:  base excision repair; damage associated molecular patterns; mitochondrial DNA; neurodegeneration; neuroinflammation
    DOI:  https://doi.org/10.3390/genes17010082
  14. Mitochondrion. 2026 Jan 25. pii: S1567-7249(26)00003-6. [Epub ahead of print]87 102113
    Serum cell-free mitochondrial DNA under a highly standardized and controlled stress induction.
    Benedict Herhaus, Carina Daubermann, Elmo W I Neuberger, Perikles Simon, Katja Petrowski.
      Cell-free mitochondrial DNA (ccf-mtDNA) is increasingly recognized as a biomarker of stress-related mitochondrial dysfunction. Acute psychological stress may induce ccf-mtDNA release, underscoring its potential role in stress physiology and adaptation. To further investigate this relationship, the present study examined acute stress-induced ccf-mtDNA dynamics in a controlled experimental setting. Twenty-seven healthy males (mean age: 23.78 ± 3.90 years) underwent both the Trier Social Stress Test (psychological stressor) and a resting condition. The kinetics of serum cell-free mitochondrial DNA (ccf-mtDNA) and serum cortisol were measured before and at 8 time points up to 105 min after the two stress conditions. After the TSST, ccf-mtDNA showed significant transient increases at +20 and +75 min, whereas cortisol exhibited the expected robust stress response. Our findings suggest that acute psychological stress can induce transient and heterogeneous changes in serum ccf-mtDNA, though these dynamics appear more modest and delayed than cortisol responses. Variability across studies underscores the need for standardized protocols and further research to clarify the mechanisms and moderators of ccf-mtDNA release under stress.
    Keywords:  Circulating cell-free mitochondrial DNA (ccf-mtDNA); Psychological stress; Trier Social Stress Test (TSST)
    DOI:  https://doi.org/10.1016/j.mito.2026.102113
  15. Geroscience. 2026 Jan 28.
    Coenzyme Q10 supplementation raises plasma levels without improving mitochondrial function in older adults.
    Malte Schmücker, Cathrine Tranberg, Jacob Borch, Mette Killerup Kaae, Michelle Damgaard, Mathias Flensted-Jensen, Ida Blom, Marco Morosetti, Sara Barbarossa, Patrick Orlando, Luca Tiano, Flemming Dela, Jørn Wulff Helge, Steen Larsen.
      Mitochondrial function is important to healthy aging, as it influences energy metabolism, oxidative stress, and physical performance. With age, mitochondrial function and biosynthesis of coenzyme Q10 (CoQ10) may change. CoQ10 serves as a key antioxidant and component of the electron transport system. Supplementation with CoQ10 may help preserve mitochondrial function and support healthy aging. Forty older community-dwelling adults (74 ± 4 years) received either daily oral CoQ10 supplementation (400 mg daily) or a placebo in a 12-week double-blinded, randomized, placebo-controlled design. Before and after the supplementation period, muscle biopsies were obtained. Subsequently, oral glucose tolerance tests (OGTT) and VO2max tests were conducted. Mitochondrial respiratory capacity (MRC), mitochondrial H2O2 emission, and mitochondrial content were assessed in both isolated mitochondria and permeabilized muscle fibers. Levels and redox status of CoQ10 were measured in plasma, muscle tissue, and isolated skeletal muscle mitochondria. Additionally, resting metabolic rate, cognitive function, and body composition were investigated. Plasma levels of CoQ10 increased significantly without changes in redox status after the intervention. No changes between groups or time were observed in muscle and isolated mitochondria regarding MRC, H2O2 emission, mitochondrial content, and levels of CoQ10. Glucose homeostasis, VO2max, and body composition were also unchanged. Twelve weeks of supplementation led to increased plasma levels of CoQ10, with unchanged levels in muscle tissue and isolated mitochondria. No differences in mitochondrial function, glucose homeostasis, and physical performance were found in a cohort of robust older adults.
    Keywords:  Antioxidant; Healthy aging; Mitochondrial function; Reactive oxygen species
    DOI:  https://doi.org/10.1007/s11357-025-02068-9
  16. Genes (Basel). 2026 Jan 03. pii: 56. [Epub ahead of print]17(1):
    Hereditary Polyneuropathies in the Era of Precision Medicine: Genetic Complexity and Emerging Strategies.
    Maria Chrysostomaki, Despoina Chatzi, Stella Aikaterini Kyriakoudi, Soultana Meditskou, Maria Eleni Manthou, Sofia Gargani, Paschalis Theotokis, Iasonas Dermitzakis.
      Hereditary polyneuropathies represent a genetically and clinically heterogeneous group of disorders affecting the peripheral nervous system, characterized by progressive motor, sensory, and autonomic impairment. Advances in molecular genetics have identified key causative genes, including PMP22, MPZ, MFN2, TTR, EGR2, and CX32 (GJB1), which are implicated in Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and related neuropathies. These conditions display substantial allelic and locus heterogeneity. Pathogenetically, mechanisms involve impaired myelin maintenance, disrupted axonal transport, mitochondrial dysfunction, and aberrant Schwann cell biology. Despite these insights, therapeutic options remain limited, and there is a pressing need to translate genetic findings into effective interventions. This review aims to provide a comprehensive synthesis of current knowledge compiling all known mutations resulting in hereditary polyneuropathies. In addition, it underscores the molecular pathomechanisms of hereditary polyneuropathies and evaluates emerging therapeutic strategies, including adeno-associated virus mediated RNA interference, CRISPR-based gene editing, antisense oligonucleotide therapy, and small-molecule modulators of axonal degeneration. Furthermore, the integration of precision diagnostics, such as next-generation sequencing and functional genomic approaches, is discussed in the context of personalized disease management. Collectively, this review underscores the need for patient-centered approaches in advancing care for individuals with hereditary polyneuropathies.
    Keywords:  Schwann cell; gene therapy; genetics; hereditary polyneuropathies; peripheral nerve; precision medicine
    DOI:  https://doi.org/10.3390/genes17010056
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