bims-mistre Biomed News
on Mito stress
Issue of 2026–06–14
nineteen papers selected by
Ellen Siobhan Mitchell, MitoQ
  1. Mitoception Via the Metabokine GDF15 and Human Health.
  2. Nutritional Regulation of Ovarian Bioenergetics: Implications for Reproductive Aging and Female Infertility.
  3. Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease.
  4. Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.
  5. Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease.
  6. DJ-1 in the Neuro-cutaneous Aging Axis: Unifying Pathways of Parkinson's Disease Neurodegeneration, Progression, and Redox-Based Therapeutic Strategies for Healthy Longevity.
  7. Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.
  8. Kaempferol as an ovarian aging-modulatory flavonol‬.
  9. Excessive training does not induce mitochondrial dysfunction or impair insulin signalling within skeletal muscle.
  10. Neurovascular coupling and energy substrate delivery in Alzheimer's disease.
  11. Editorial: Mitochondrial dysfunction in cellular and molecular mechanisms of brain aging.
  12. Evaluating a Coenzyme Q10-Based Food for Special Medical Purpose, for Mitochondrial Diseases Management: An Open-Label, Pilot Trial.
  13. Current Evidence of Acetyl-L-Carnitine Use in Mood Disorders-: A Systematic Review and Meta-Analysis.
  14. EGCG Protects Mouse Oocytes from Malathion-Induced Damage by Preserving Mitochondrial Function, Genomic Integrity, and Fertilization Competence.
  15. Mitochondrial enzyme dysfunction in Alzheimer's disease: a systematic review of human metabolic evidence.
  16. STING1 senses mitochondrial damage to promote mitophagy.
  17. 17β-estradiol mitigates ovariectomy-induced defects in mitochondrial bioenergetics and redox balance after VML injury in female mice.
  18. Differences in functional connectivity during midlife between menopause stages.
  19. Comparative Efficacy of Nutraceuticals on Endothelial Function: A Systematic Review and Network Meta-Analysis.
  1. Biopsychosoc Sci Med. 2026 Jun 09.
    Mitoception Via the Metabokine GDF15 and Human Health.
    Cynthia C Liu, Qiuhan Huang, Evan D Shaulson, Caroline Trumpff, Elissa Epel, Lisa Feldman Barrett, Daniel W Belsky, Maxwell Z Wilson, Alan A Cohen, Eugene Mosharov, Nirosha J Murugan, Tor D Wager, Martin Picard.
      To survive and thrive, living organisms must monitor and regulate cell-level energy supply, demand, and transformation. Metabolic energy is monitored through a set of brain-directed interoceptive processes we refer to as metaboception. Here, we review evidence for a specific metaboceptive signaling cascade mediated by the cytokine/metabokine growth differentiation factor 15 (GDF15), which we refer to as mitoception. Mitoception involves an afferent signaling arm initiated by the integrative stress response within cells, and an efferent signaling arm that simultaneously promotes systemic energy conservation and fuel mobilization. Afferent mitoceptive signaling is mediated by GDF15 released when cells face energy demand in excess of their energy transformation capacity, creating an energy gap. The efferent arm of mitoceptive signaling arises when GDF15 receptors in the brainstem receive the signal and initiate psychological experiences including fatigue and anxiety, together with neuroendocrine stress responses. Mitoceptive outputs thus reprioritize systemic energy metabolism to promote allostasis, survival, and long-term health. This article is an introduction to GDF15 psychobiology, and proposes a GDF15-driven mitoception cascade that makes predictions about modifiable processes shaping disease risk, mental health, mood, resilience, well-being, and aging.
    Keywords:  GDF15; anxiety; behaviors; bioenergetics; energetic pain; fatigue; metaboception; mitoception; stress-disease cascade
    DOI:  https://doi.org/10.1097/PSY.0000000000001498
  2. Nutrients. 2026 May 30. pii: 1773. [Epub ahead of print]18(11):
    Nutritional Regulation of Ovarian Bioenergetics: Implications for Reproductive Aging and Female Infertility.
    Jihyun Kim, Jaewang Lee.
      Ovarian function is critically dependent on tightly coordinated cellular energy metabolism, which governs follicular development, oocyte competence, and reproductive longevity. Increasing evidence indicates that metabolic dysregulation, including mitochondrial dysfunction, oxidative imbalance, and impaired NAD+ metabolism, contributes to the pathophysiology of major ovarian disorders such as PCOS, ovarian aging, and DOR. In parallel, emerging studies suggest that nutritional factors influence ovarian function by modulating mitochondrial bioenergetics, redox homeostasis, and nutrient-sensing signaling pathways. This review summarizes current knowledge on the molecular basis of ovarian energy metabolism and its disruption in female reproductive disorders. We further discuss nutritional strategies targeting ovarian bioenergetics, including antioxidants, NAD+ precursors, mitochondrial cofactors, and dietary metabolic interventions. In addition, we highlight recent advances in metabolomics, microbiome research, epigenomics, and multi-omics integration that are shaping emerging nutrition-based approaches in reproductive medicine. Collectively, positioning ovarian metabolism at the center of nutritional reproductive research may provide a conceptual framework for understanding metabolic regulation in ovarian function and for guiding future research on reproductive health.
    Keywords:  NAD+ metabolism; mitochondrial dysfunction; nutritional intervention; ovarian metabolism; reproductive aging
    DOI:  https://doi.org/10.3390/nu18111773
  3. Int J Mol Sci. 2026 May 30. pii: 4966. [Epub ahead of print]27(11):
    Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease.
    Hanna Bynum, Kristin S Edwards.
      Mitochondria are central regulators of cellular bioenergetics, redox balance, and signaling pathways that integrate metabolic and immune responses. Emerging evidence indicates that biological sex is an important determinant of mitochondrial function, in part through the regulatory effects of sex hormones on mitochondrial biogenesis, oxidative phosphorylation, reactive oxygen species production, and quality control mechanisms. Estrogen, testosterone, and progesterone differentially modulate mitochondrial dynamics, substrate utilization, antioxidant capacity, and immune signaling, resulting in distinct mitochondrial phenotypes that may influence disease susceptibility across the lifespan. In this review, we synthesize current knowledge on the mechanistic basis of sex differences in mitochondrial function and highlight mitochondria as key mediators linking endocrine signaling to immunometabolic regulation. We discuss how mitochondrial-derived signals, including mitochondrial reactive oxygen species, mitochondrial DNA release, and cardiolipin exposure, activate inflammatory pathways such as NF-κB, cGAS-STING, and NLRP3 inflammasome signaling. These pathways may contribute to chronic inflammation, gut barrier dysfunction, and systemic metabolic disruption. We further examine the impact of major endocrine transitions, including pregnancy, the postpartum period, menopause, and androgen imbalance in conditions such as polycystic ovary syndrome, on mitochondrial function and disease risk. Particular emphasis is placed on the gastrointestinal tract as a metabolically active and mitochondria-dependent interface, where mitochondrial dysfunction may contribute to epithelial barrier disruption, microbial dysbiosis, and systemic inflammation. Finally, we discuss emerging therapeutic strategies targeting mitochondrial function, including exercise, hormone-based therapies, mitochondria-targeted antioxidants, and interventions aimed at improving mitochondrial quality control. Understanding sex-specific mitochondrial regulation may provide a framework for improved endocrine stratification, mitochondrial phenotyping, and precision medicine approaches across diverse clinical contexts.
    Keywords:  endocrine disorders; estrogen; immunometabolism; mitochondria; mitochondrial dynamics; mitochondrial reactive oxygen species; oxidative phosphorylation; sex differences; sex hormones; testosterone
    DOI:  https://doi.org/10.3390/ijms27114966
  4. Cells. 2026 May 28. pii: 990. [Epub ahead of print]15(11):
    Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.
    Jasbir Bisht, Priyanka Rawat, Andrew C Shin, Vijay Hegde.
      Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by progressive cognitive decline due to the loss of neurons. The accumulation of extracellular senile plaques (Aβ) and intracellular tau neurofibrillary tangles (NFTs) is a key pathological feature of AD. Mitochondrial dysfunction is implicated in all key AD pathologies, whether as a cause or a consequence of disease progression. Growing evidence indicates that mitochondrial impairment plays a central role in AD pathogenesis by disrupting cellular homeostasis, promoting oxidative stress, and contributing to progressive neuronal death. Therefore, targeting mitochondria may offer promising insights into the development of disease-modifying therapies. In this review, we summarize current evidence on the role of mitochondrial dysfunction in the pathophysiology of AD and on its therapeutic potential.
    Keywords:  Alzheimer’s disease; mitochondrial dysfunction; mitochondrial therapeutics; neurodegenerative disease; neuronal loss; oxidative stress
    DOI:  https://doi.org/10.3390/cells15110990
  5. Commun Biol. 2026 Jun 10.
    Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease.
    Purba Mandal, Eugenia Trushina, Matthias Arnold, Rima Kaddurah-Daouk, Priyanka Baloni.
      Asymptomatic Alzheimer's disease (AsymAD) refers to individuals who, despite exhibiting amyloid-β plaques and tau pathology comparable to Alzheimer's disease (AD), maintain cognitive performance similar to cognitively normal individuals. The resilience mechanism in AsymAD individuals remains understudied. We performed a systematic analysis comparing AsymAD and AD across multiple cohorts (ROSMAP, Banner and Mount Sinai), brain regions (BA6, BA9, BA36 and BA37) and neuronal and glial cell types using proteomics and transcriptomics data. AsymAD brains exhibited preserved mitochondrial bioenergetics, characterized by enhanced oxidative phosphorylation, electron transport chain activity, fatty acid and lipid metabolism, and branched-chain amino acid utilization. Pathways regulating mitochondrial complex biogenesis and calcium homeostasis were also upregulated. Key mitochondrial proteins such as MRPL47, CPT2, BCAT2, and IDH2, were consistently upregulated in AsymAD. At the cellular level, excitatory neurons, including superficial, mid-layer, and deep-layer subtypes, exhibited the most preserved mitochondrial function, whereas vulnerable inhibitory subtypes, including PVALB and SST neurons, showed increased cellular abundance and bioenergetic activity. In contrast, microglia and oligodendrocytes proportions were reduced in AsymAD relative to AD. Our findings identify preserved mitochondrial bioenergetics in AsymAD and suggest that enhancing NADH metabolism via NAD+ precursor-based interventions may potentially help in maintaining cognitive function despite amyloid and tau pathology.
    DOI:  https://doi.org/10.1038/s42003-026-10474-8
  6. Mol Neurobiol. 2026 Jun 08. pii: 683. [Epub ahead of print]63(1):
    DJ-1 in the Neuro-cutaneous Aging Axis: Unifying Pathways of Parkinson's Disease Neurodegeneration, Progression, and Redox-Based Therapeutic Strategies for Healthy Longevity.
    Azhagu Madhavan Sivalingam.
      Sleep and circadian disturbances precede motor symptoms in Parkinson's disease (PD), acting as early neurodegeneration indicators. Disrupted rhythms, mitochondrial dysfunction, neuroinflammation, and neurotransmitter imbalance create a self-reinforcing cycle that accelerates progression. DJ-1 (PARK7), a redox-sensitive protein, provides central neuroprotection by preserving mitochondrial integrity, mitigating oxidative stress, and curbing neuroinflammation. DJ-1 loss or mutation weakens antioxidant defences, promotes α-synuclein aggregation, and worsens dopaminergic neuron loss, positioning it as a key biomarker and therapeutic target. Oxidative stress, mitochondrial impairment, chronic inflammation, and telomere attrition link neurodegeneration to systemic and skin aging via a "neuro-cutaneous aging axis." Similar mechanisms include mitochondrial dysfunction, ferroptosis, and redox imbalance energy Alzheimer's cognitive decline. Chronotherapy, NRF2 activators, phytochemicals, nanozymes, and postbiotics offer promise in restoring redox balance and halting progression. Telomere dysfunction and genomic instability further connect neural and skin aging, modulated by environment, diet, and lifestyle. Micro physiological systems, predictive analytics, and personalized medicine enhance mechanistic insights and therapy development. Targeting interconnected pathways of redox regulation, mitochondrial function, proteostasis, and telomere maintenance provides a unified approach to combat neurodegeneration and aging. DJ-1-focused therapies, paired with antioxidants and mitochondrial interventions, hold strong potential for disease modification and healthy aging.
    Keywords:  DJ-1 (PARK7); NRF2 pathway; Neurodegeneration; Oxidative stress; Skin aging
    DOI:  https://doi.org/10.1007/s12035-026-05981-y
  7. MedComm (2020). 2026 Jun;7(6): e70790
    Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.
    Zijie Xiang, Yu Chen, Xishui Liu, Haowen Lu, Yuqing Yang, Lei Xing, Yu Zhang, Chuandong Lang, Siming Zhang, Shixiang Zhao, Youzhi Hong, Jiaxiang Bai, Yusen Qiao.
      Aging is a complex biological process characterized by the functional decline of multiple cellular organelles, with mitochondrial dysfunction emerging as a predominant hallmark. Alterations in mitochondria within senescent cells primarily encompass two interrelated aspects: intrinsic mitochondrial dysfunction and compromised mitochondrial quality control systems, including mitophagy, dynamics, and biogenesis. However, a comprehensive synthesis that bridges mechanistic insights into mitochondrial dysfunction with an analysis of therapeutic obstacles remains lacking. Here, we systematically summarized the pathways leading to mitochondrial dysfunction in aging and deeply analyzed how this dysregulation, including mitochondrial DNA instability and mitochondria driving inflammation through the cGAS-STING pathway, contributed to the etiology of aging-related diseases, including muscle, bone, neurodegeneration, cardiovascular, and metabolic diseases. Additionally, we analyzed a series of mitochondrial targeted treatment strategies, from metabolism and kinetic regulation to disease-specific intervention and emerging technologies, such as mitochondrial transplantation and mitochondrial DNA base editing. Finally, we emphasized the key obstacles that must be overcome for clinical transformation, including tissue-specific mitochondrial heterogeneity. By combining the basic mechanism with the development of treatment and its potential challenges, this review provides a key perspective for promoting the emerging field of mitochondrial medicine to intervene in aging-related pathology more accurately and effectively.
    Keywords:  aging; mitochondria; therapy
    DOI:  https://doi.org/10.1002/mco2.70790
  8. Biogerontology. 2026 Jun 08. pii: 112. [Epub ahead of print]27(4):
    Kaempferol as an ovarian aging-modulatory flavonol‬.
    Hamid Reza Nejabati, Leila Roshangar.
      Kaempferol (KMP) is a dietary compound found in a wide range of foods. The therapeutic capabilities of these foods are associated with the phenolic compounds present in their structures, particularly their antioxidant activity. Remarkable medical care areas linked to KMP include pain relief, anti-aging, antiallergic, anticancer, antidiabetic, anti-inflammatory, antioxidant, antipyretic, central nervous system regulation, wound healing, and hepatoprotective characteristics. KMP has attracted considerable attention in the examination of its possible roles in dealing with a range of age-related diseases. These conditions include cardiovascular diseases (CVDs), immunoinflammatory diseases, neurodegenerative diseases (NDs), and cancer. It can delay oocyte aging, thereby enhancing the subsequent embryonic growth cascade. Delaying oocyte aging is mainly accomplished by reducing apoptosis and reactive oxygen species (ROS) levels. Furthermore, KMP has antioxidant effects on age-related diminished ovarian reserve (AR-DOR) by reducing HSP90 expression, thereby boosting NRF2 expression. KMP treatment influences multiple processes in aging oocytes, including peroxisome function, oxidative stress, cAMP signaling, TNF signaling, and gap junction pathways. Additionally, KMP improved negative pregnancy outcomes associated with fertilized aged oocytes.
    Keywords:  Hormesis; Hormetin; Kaempferol; Ovarian aging
    DOI:  https://doi.org/10.1007/s10522-026-10460-x
  9. J Physiol. 2026 Jun 11.
    Excessive training does not induce mitochondrial dysfunction or impair insulin signalling within skeletal muscle.
    Geneviève J DesOrmeaux, Henver S Brunetta, Pierre-Andre Barbeau, Alexandra M Coates, Christopher Pignanelli, Fasih A Rahman, Jamie F Burr, Graham P Holloway.
      Excessive training, also known as overtraining, has been suggested to impair skeletal muscle mitochondrial function and glucose homeostasis, challenging the notion that exercise is inherently beneficial. However, methodological limitations on assessment of mitochondrial bioenergetics while considering exercise-induced mitochondrial biogenesis make the metabolic consequences of overtraining still debatable. Therefore, we investigated skeletal muscle insulin signalling and mitochondrial bioenergetics in skeletal muscle following a 3-week overtraining protocol in healthy highly trained endurance athletes. Proteomics of skeletal muscle revealed an upregulation of proteins related to fatty acid metabolism and mitochondrial content induced by overload training. Functionally, mitochondrial respiratory capacity as well as H2O2 emission were increased in permeabilized muscle fibres. These effects were dependent on mitochondrial content, suggesting preservation of intrinsic mitochondrial oxidative phosphorylation. While sub-maximal mitochondrial H2O2 emission and oxidative stress were increased following excessive training, insulin signalling within skeletal muscle (i.e., Akt phosphorylation) during an oral glucose challenge was improved, suggesting excessive exercise does not induce skeletal muscle insulin resistance. In a further analysis, based on their psycho-physiological performances, participants were identified by who successfully or not developed an overreaching phenotype. This approach revealed a unique proteome signature in individuals who were overreached, marked by a smaller increase in proteins involved in cytoskeleton organization, glycogen metabolism, and protein translation. However, despite such classification, we did not observe reductions in either mitochondrial bioenergetics or insulin signalling within skeletal muscle. Altogether, overtraining in highly active individuals induces mitochondrial biogenesis without impairments in skeletal muscle insulin signalling nor mitochondrial oxidative capacity. KEY POINTS: Proteomics revealed upregulation of fatty acid and mitochondrial proteins by excessive training. Overtraining does not cause mitochondrial dysfunction. Improved insulin signalling in skeletal muscle post-overtraining. Overreached athletes show blunted increase in protein synthesis and metabolism.
    Keywords:  glucose; metabolism; overtraining; proteome; skeletal muscle
    DOI:  https://doi.org/10.1113/JP289538
  10. Int Rev Neurobiol. 2026 ;pii: S0074-7742(26)00029-2. [Epub ahead of print]186 317-338
    Neurovascular coupling and energy substrate delivery in Alzheimer's disease.
    Shivam Malviya, Debasmita Saha, Anagha Kamble, Divya Ramesh Singh, Sivaraj Mohana Sundaram, Vasudharani Devanathan.
      The brain has exceptionally high metabolic demands and depends on a continuous supply of oxygen and glucose to maintain neuronal activity and cognitive function. Despite accounting for only about 2 % of body weight, it consumes more than 20 % of the body's energy. This demand is met through tightly regulated cerebral blood flow mediated by neurovascular coupling (NVC), a process that links neuronal activity with local vascular responses. The cellular components responsible for this regulation including neurons, astrocytes, endothelial cells, pericytes, and vascular smooth muscle cells form the neurovascular unit (NVU), which maintains blood brain barrier (BBB) integrity, metabolic homeostasis, and efficient substrate delivery. Increasing evidence suggests that disruption of neurovascular and metabolic regulation is an early and critical contributor to Alzheimer's disease (AD). Impairment of NVU function leads to reduced cerebral blood flow, endothelial dysfunction, pericyte loss, and breakdown of the BBB. These vascular changes compromise the delivery of oxygen and glucose, resulting in cerebral hypometabolism that often precedes classical pathological hallmarks such as amyloid-β plaques and tau neurofibrillary tangles. Alterations in glucose transport across the BBB, particularly reduced expression of the GLUT1 transporter, further exacerbate neuronal energy deficits. Disturbances in lactate metabolism and mitochondrial dysfunction also contribute to oxidative stress and progressive neurodegeneration. Understanding the interaction between neurovascular dysfunction, impaired brain metabolism, and AD pathology provides important insight into disease progression. Therapeutic strategies aimed at restoring vascular function, improving metabolic substrate delivery, and enhancing neuronal energy metabolism may offer promising avenues for early intervention in AD.
    Keywords:  Blood brain barrier; Brain glucose metabolism; Cerebral blood flow; Cerebral hypometabolism; GLUT1 transporter; Neurovascular coupling; Neurovascular unit
    DOI:  https://doi.org/10.1016/bs.irn.2026.05.001
  11. Front Aging Neurosci. 2026 ;18 1866752
    Editorial: Mitochondrial dysfunction in cellular and molecular mechanisms of brain aging.
    Ying Li, Aswathy Peethambaran Mallika, Meghraj Singh Baghel, Bhupendra V Shravage, Pei Shang.
      
    Keywords:  Alzheimer's disease; Parkinson's disease; aging; mitochondria; oxidative phosphorylation (OXPHOS)
    DOI:  https://doi.org/10.3389/fnagi.2026.1866752
  12. Int J Mol Sci. 2026 Jun 05. pii: 5127. [Epub ahead of print]27(11):
    Evaluating a Coenzyme Q10-Based Food for Special Medical Purpose, for Mitochondrial Diseases Management: An Open-Label, Pilot Trial.
    Lucia Chico, Piervito Lopriore, Giulia Cecchi, Adriana Meli, Clara Bernardini, Linda Balestrini, Maico Polzella, Vincenzo Montano, Michelangelo Mancuso.
      Primary mitochondrial diseases (PMD) are rare disorders with limited therapeutic options. Coenzyme Q10 (CoQ10) supplementation is widely used, although formulation differences can affect absorption and efficacy. This open-label pilot feasibility trial evaluated a food for special medical purposes (FSMP) containing high-dose CoQ10 (250 mg per capsule) in patients with PMD. Ten patients (mean age: 55.5 ± 8.6 years) were enrolled. Serum/plasma biomarkers, including CoQ10, fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), ferric-reducing antioxidant power (FRAP), total sulfhydryl groups (t-SH), and advanced oxidation protein products (AOPP), were assessed at baseline (T0, after ≥30 days of conventional ubidecarenone) and after 30 days of FSMP administration (T1). Fatigue severity scale (FSS) and 5-times sit-to-stand test (5xSST) were evaluated at both timepoints. FSMP was administered at 250 or 500 mg/day. Twenty sex- and age-matched healthy controls were included for CoQ10 comparison. Absolute CoQ10 concentrations remained stable overall at T1, with all patients maintaining levels above 390 ng/mL (100% vs. 60% at T0), although concentrations remained lower than in healthy controls (p < 0.01). Dose-normalized CoQ10 exposure was significantly higher with FSMP versus conventional ubidecarenone (p < 0.001, Cohen's d = 7.31). FGF21, GDF15, AOPP, and t-SH remained unchanged, whereas FRAP increased at T1 (p < 0.01). No significant changes were observed in 5xSST and FSS. Exploratory analyses indicated inter-individual variability in functional responses. FSMP was associated with higher dose-normalized systemic CoQ10 exposure, more consistent circulating CoQ10, and increased FRAP levels. Its simplified dosing regimen may support long-term adherence. Larger studies are warranted to validate these preliminary findings.
    Keywords:  antioxidants; coenzyme Q10; food for special medical purposes; mitochondrial diseases
    DOI:  https://doi.org/10.3390/ijms27115127
  13. Neuropsychiatr Dis Treat. 2026 ;22 586506
    Current Evidence of Acetyl-L-Carnitine Use in Mood Disorders-: A Systematic Review and Meta-Analysis.
    Rakesh Kumar, Zahra Hashempour, Sara Shahriarirad, Reza Shahriarirad, Leslie C Hassett, Balwinder Singh, Paul E Croarkin, Marin Veldic, Mark A Frye, Sandeep R Pagali.
      Acetyl-l-carnitine (ALC) is increasingly recognized for its potential psychopharmacological mechanism and role in the treatment of mood disorders, particularly major depressive disorder (MDD) and bipolar disorder (BD). Emerging evidence suggests that ALC levels are reduced in individuals with MDD, and this deficiency may contribute to depressive symptoms through disruptions in mitochondrial fatty acid transport, neuroplasticity, and neurotransmission. This review synthesizes findings from randomized controlled trials, open-label studies, and observational research examining ALC use and clinical outcomes in adults treated with ALC in MDD and BD. A systematic review (n=15) and meta-analysis (n=10) studies (14 randomized controlled trials [RCTs] and 1 open label) involving 809 participants (treatment group: 392; comparator group: 417) revealed that ALC significantly reduces depressive symptoms compared to placebo, with comparable efficacy to standard antidepressants and fewer adverse effects. Subgroup analyses suggest enhanced benefits in older adults and those with treatment-resistant depression. These findings support the potential of ALC as both a biomarker and a therapeutic agent in mood disorders. Further large-scale, longitudinal studies are needed to clarify its clinical utility and mechanistic pathways in mood disorders.
    Keywords:  ALC; acetyl-L-carnitine; bipolar depression; major depressive disorders; mood disorders; personalized medicine
    DOI:  https://doi.org/10.2147/NDT.S586506
  14. Reprod Toxicol. 2026 Jun 11. pii: S0890-6238(26)00125-5. [Epub ahead of print] 109282
    EGCG Protects Mouse Oocytes from Malathion-Induced Damage by Preserving Mitochondrial Function, Genomic Integrity, and Fertilization Competence.
    Miao Hu, Xiaopeng Wang, Kaiyue Zhang, Huachao Gao, Zhao-Jia Ge, Shen Yin.
      Organophosphate pesticides such as malathion (Mal) pose a significant threat to female reproductive health, primarily by impairing oocyte quality, yet effective protective countermeasures remain limited. This study investigated whether epigallocatechin gallate (EGCG), a green tea polyphenol with known antioxidant properties, could protect oocytes by targeting mitochondrial function, a key mechanism implicated in its toxicity. Using a mouse in vitro oocyte maturation model, we demonstrate that Mal exposure severely disrupts both nuclear maturation, indicated by suppressed polar body extrusion, and cytoplasmic maturation. The toxicity manifests through a defined mitochondrion-centric pathological cascade: Mal induces the loss of mitochondrial membrane potential (ΔΨm), which in turn triggers excessive reactive oxygen species (ROS) production and activates early apoptosis. At the transcriptional level, Mal induced the disordered mitochondrial biogenesis, impaired Nrf2-mediated antioxidant signaling and activated apoptotic pathways. These subcellular injuries lead to profound functional and structural defects, including DNA damage accumulation (γ-H2AX foci), meiotic spindle disruption, chromosome misalignment, and loss of Juno protein on the oocyte surface, ultimately resulting in a significantly reduced sperm-binding capacity. Importantly, co-treatment with EGCG effectively mitigated this entire cascade. EGCG preserved ΔΨm, suppressed oxidative stress and apoptosis, by normalizing these transcriptional alterations to improve mitochondrial biogenesis, antioxidant capacity and anti-apoptotic status. EGCG restored Juno expression, reduced DNA damage, maintained spindle integrity, and improved fertilization competence. Our findings demonstrate that EGCG rescues Mal-induced oocyte damage primarily by preserving mitochondrial integrity, Nrf2-dependent antioxidant defense and apoptotic signaling, thereby safeguarding both cytoplasmic maturation and nuclear genomic stability. This highlights its potential as a mitochondrion-targeting nutraceutical strategy to counteract reproductive toxicity from environmental pesticides.
    Keywords:  EGCG; Malathion; Mitochondrial dysfunction; Oocyte
    DOI:  https://doi.org/10.1016/j.reprotox.2026.109282
  15. Metab Brain Dis. 2026 Jun 10. pii: 132. [Epub ahead of print]41(1):
    Mitochondrial enzyme dysfunction in Alzheimer's disease: a systematic review of human metabolic evidence.
    Mahsa Asadi Anar, Mohammad Amin Fathollahi, Fereshteh Zare, Zahra Farrokhi, Elham Habibzadeh, Saina Hasany, Majid Mirmazloumi, Melika Arab Bafrani, Fatemeh Abedian Kenari, Marjan Falahati, Kamyar Khorsand, Amirali Zakavi, Yasaman Asadollah Salmanpour, Elham Yadegarifard, Farbod Khosravi, Parsa Goudarzi.
      Alzheimer's disease (AD) is characterized by progressive cognitive decline accompanied by profound disturbances in cerebral energy metabolism. Mitochondrial dysfunction has long been implicated in AD pathophysiology; however, the specific contribution of mitochondrial enzymes in human disease remains fragmented across heterogeneous studies. Enzymes regulating carbon entry into the tricarboxylic acid cycle, oxidative phosphorylation, and redox balance represent key metabolic control points whose dysfunction may contribute to neuronal vulnerability. To systematically synthesize human evidence on mitochondrial enzyme alterations in Alzheimer's disease and to evaluate the feasibility of quantitative meta-analysis based on current reporting practices. A systematic literature search was conducted in PubMed, Scopus, and Web of Science from database inception through January 2026 in accordance with PRISMA 2020 guidelines. Studies were included if they investigated mitochondrial enzymes in human postmortem brain tissue, human-derived cellular models, or peripheral biospecimens. Risk of bias was assessed using the ROBINS-I tool. The feasibility of meta-analysis was evaluated based on the availability and comparability of group-level summary statistics. Fifteen studies met the eligibility criteria and were included in the final synthesis. Mitochondrial enzymes involved in carbon entry into the tricarboxylic acid cycle, oxidative phosphorylation, redox regulation, and neurotransmitter-linked mitochondrial metabolism were the most frequently investigated targets. Direct enzyme-activity evidence most consistently implicated selected metabolic control points, particularly PDHC and αKGDHC, whereas additional studies supported mitochondrial impairment through protein or post-translational modification changes, respiratory dysfunction, redox alterations, or RNA-regulatory mechanisms. Quantitative meta-analysis was not feasible due to heterogeneous assay methodologies, variable normalization strategies, and inconsistent reporting of group-level summary statistics. Human evidence consistently implicates mitochondrial enzyme dysfunction as a central metabolic feature of Alzheimer's disease. However, progress toward cumulative quantitative synthesis remains limited by methodological heterogeneity and incomplete reporting of enzyme activity outcomes. Standardized measurement and reporting of mitochondrial enzyme alterations will be essential to advance mechanistic understanding and enable future meta-analytic integration.
    Keywords:  Alzheimer’s disease; Mitochondrial enzymes; Neurodegeneration; Oxidative phosphorylation; Tricarboxylic acid cycle
    DOI:  https://doi.org/10.1007/s11011-026-01895-9
  16. Autophagy. 2026 Jun 13.
    STING1 senses mitochondrial damage to promote mitophagy.
    Ze-Bo Huang, Jin-Yi Lin, Ling-Jun Cheng, Hayden Weng Siong Tan, Han-Ming Shen, Guang Lu.
      The cGAS-STING1 pathway is essential for innate immunity, while its functions beyond immune activation have emerged as a key research topic. Recent studies have revealed the non-canonical roles of this pathway in autophagy. However, whether it participates in organelle quality control through selective autophagy processes such as mitophagy remains largely unexplored. In our study, we identify the cGAS-STING1 pathway as an essential upstream regulator of PINK1-PRKN-dependent mitophagy. We demonstrate that upon mitochondrial damage, STING1 is recruited to damaged mitochondria in a process requiring PINK1- and VCP/p97-mediated degradation of outer mitochondrial membrane proteins. STING1 at damaged mitochondria then activates TBK1, which phosphorylates the mitophagy receptor OPTN at Ser177, enhancing its recruitment to damaged mitochondria and driving efficient mitophagy. Disruption of the STING1-TBK1-OPTN axis impairs mitophagy and shifts the cellular response from pro-survival mitophagy to apoptosis. Our findings therefore uncover a non-canonical, pro-survival function of the cGAS-STING1 pathway in mitophagy, extending its role beyond innate immunity to the regulation of selective autophagy and cell fate decisions. Abbreviations: BafA1: bafilomycin A1; cGAS: cyclic GMP‑AMP synthase; ER: endoplasmic reticulum; GABARAP: GABA type A receptor-associated protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MQC: mitochondrial quality control; mtDNA: mitochondrial DNA; NAC: N-Acetylcysteine; Nec-1: Necrostatin-1; OMM: outer mitochondrial membrane; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RIPK1: receptor interacting serine/threonine kinase 1; ROS: reactive oxygen species; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; VCP/p97: valosin containing protein; Z-VAD-FMK: benzyloxycarbony (Cbz)-l-ValAla-Asp (OMe)-fluoromethylketone.
    Keywords:  Cell death; OPTN; PINK1-PRKN-dependent mitophagy; cGAS-STING1 pathway; innate immunity; mitochondrial quality control
    DOI:  https://doi.org/10.1080/15548627.2026.2689463
  17. Am J Physiol Cell Physiol. 2026 Jun 11.
    17β-estradiol mitigates ovariectomy-induced defects in mitochondrial bioenergetics and redox balance after VML injury in female mice.
    Junwon Heo, David L Miller, Jessica R Hoffman, Reese M Groover, Sarah M Greising, Jarrod A Call.
      Volumetric muscle loss (VML) is characterized by an irrecoverable loss of skeletal muscle mass, persistent functional deficits, and metabolic dysfunction. A disrupted cellular redox homeostasis is one attribute of this metabolic dysfunction and can lead to excessive reactive oxygen species (ROS) emissions and chronic oxidative stress. The primary objective of this study was to define the role of ovarian hormones, specifically 17β-estradiol (17β-E2), in driving mitochondrial bioenergetic and redox balance after VML injury. Female C57BL/6J mice were randomized into experimental and control groups (VML-sham OVX, VML-OVX, and VML-OVX-E2). A time course of ROS emissions and antioxidant buffering capacity (AoxBC) for VML-injured muscles was established across the first 60 days post-injury (dpi) in ovary-intact females. Ovariectomy (OVX) was performed prior to injury to deplete ovarian hormones, and 17β-E2 was administered via continuous-release pellets to investigate the effects of hormone loss and repletion on ROS emissions and mitochondrial bioenergetics. The long-term effects of 17β-E2 were evaluated to determine whether restoring redox led to sustained redox balance long-term. Transcriptomic analyses were conducted to explore molecular mechanisms of 17β-E2 benefit after VML. In intact females, ROS emissions were greater during the first 14-dpi, but AoxBC recovered more rapidly than previously observed in males. OVX exacerbated VML-induced metabolic dysfunction, resulting in less AoxBC, greater ROS emissions, and an early suppression of mitochondrial gene networks. 17β-E2 repletion attenuated ROS emissions and improved AoxBC at 7-dpi, and led to greater mitochondrial respiratory capacity, conductance, and bioenergetic efficiency out to 60-dpi. Chronic 17β-E2 depletion resulted in impaired glucose tolerance and greater adiposity, which were mitigated by 17β-E2 treatment. Transcriptomic analyses suggest that 17β-E2 contributes to resolving inflammation and enforcing a temporal decoupling of cellular expansion and mitochondrial maturation after VML injury.
    Keywords:  Estrogen Receptors; Metabolic Flexibility; Muscle Trauma; Regenerative Medicine; Sex as a Biological Variable (SABV)
    DOI:  https://doi.org/10.1152/ajpcell.00282.2026
  18. Menopause. 2026 Jun 09.
    Differences in functional connectivity during midlife between menopause stages.
    Abigail A Testo, Julie A Dumas.
       OBJECTIVE: Our goal was to assess the relationship between menopause stage and resting-state functional connectivity during midlife.
    METHODS: Data from the Human Connectome Project-Aging 2.0 release were utilized in this study. Imaging and demographic data of 151 female participants between 40 and 55 years of age were included. To investigate functional connectivity, we utilized Conn Toolbox to assess the strength of functional associations between brain regions at rest at both connection and cluster levels.
    RESULTS: Differences in resting-state functional connectivity between the supramarginal gyrus, right anterior division, and right planum temporale at the connection level were identified between participants in the pre-, peri-, and postmenopausal groups when all groups were compared. Further analysis comparing the pre- and postmenopausal groups revealed one cluster of altered resting-state connectivity that was lower in the postmenopausal group compared to the premenopausal group. Regions with altered connectivity included the left and right supramarginal gyrus, the anterior division, and the right and left planum temporale.
    CONCLUSIONS: Resting-state functional connectivity differed between menopause stages, highlighting the relationship between menopause and brain functioning during midlife in females. Differences in functional connectivity between pre- and postmenopausal participants suggest that the menopause transition may be relevant to brain functioning during the female aging process.
    Keywords:  Functional connectivity; Menopause; Midlife; fMRI
    DOI:  https://doi.org/10.1097/GME.0000000000002836
  19. Curr Atheroscler Rep. 2026 Jun 12. pii: 62. [Epub ahead of print]28(1):
    Comparative Efficacy of Nutraceuticals on Endothelial Function: A Systematic Review and Network Meta-Analysis.
    Mostafa Norouzzadeh, Minoo Hasan Rashedi, Ghazaleh Mahdavi-Mazdeh, Ali Kosari, Hossein Shahinfar.
       PURPOSE OF REVIEW: This network meta-analysis (NMA) compares the efficacy of dietary interventions in improving flow mediated dilation (FMD) as a measure of endothelial function among individuals with cardiovascular diseases (CVDs) and hypertension. This work can be a basis for the design of future clinical trials and for the development of evidence-based nutritional guidelines to improve cardiovascular outcomes.
    RECENT FINDINGS: The most substantial improvements in FMD were observed with magnesium (MD: 8.17; CoE: High), vitamin D3 (MD: 7.84; CoE: High), flaxseed (MD: 7.39; CoE: Low), barberry (MD: 6.64; CoE: Moderate), folic acid (MD: 3.36; CoE: Low), and omega-3 (MD: 1.83; CoE: Very low). Sensitivity analyses confirmed the robustness of these findings. Several dietary interventions, particularly magnesium and vitamin D₃, have been shown to improve endothelial function in individuals with CVDs and hypertension. These findings highlight the potential role of nutritional strategies as adjunct therapies for preserving vascular health.
    TRIAL REGISTRATION: Systematic review registered with PROSPERO, registration number CRD420251041093.
    Keywords:  Coronary Disease; Dietary Supplements; Heart Failure; Myocardial Infarction; Preventive Medicine; Vascular Diseases
    DOI:  https://doi.org/10.1007/s11883-026-01436-w
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