bims-mitrat 2024-04-21 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2024–04–21
fifteen papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Platelet-derived microparticles and their cargos: The past, present and future.
Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.
Focusing on mitochondria in the brain: from biology to therapeutics.
Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.
Delineating the contribution of ageing and physical activity to changes in mitochondrial characteristics across the lifespan.
Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.
Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.
Extracellular vesicles and their therapeutic applications: a review article (part1).
Human umbilical cord mesenchymal stem cell-derived exosomes alleviate the severity of experimental autoimmune encephalomyelitis and enhance lag-3 expression on foxp3 + CD4 + T cells.
The Role of Extracellular Vesicles in the Treatment of Prostate Cancer.
PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration.
Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.
Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.
Extracellular mitochondrial components as new biomarkers for lupus nephritis.
Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Asian J Pharm Sci. 2024 Apr;19(2): 100907

Platelet-derived microparticles and their cargos: The past, present and future.

Jingwen Guo, Bufeng Cui, Jie Zheng, Chang Yu, Xuran Zheng, Lixin Yi, Simeng Zhang, Keke Wang.

  All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

Keywords:  Application; Heterogeneity; Platelet-derived particles; Potential and limitations

DOI:  https://doi.org/10.1016/j.ajps.2024.100907
bioRxiv. 2024 Apr 03. pii: 2024.04.02.587832. [Epub ahead of print]

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Dong Liu, Hannah C Webber, Fuyun Bian, Yangfan Xu, Manjari Prakash, Xue Feng, Ming Yang, Hang Yang, In-Jee You, Liang Li, Liping Liu, Pingting Liu, Haoliang Huang, Chien-Yi Chang, Liang Liu, Sahil H Shah, Anna La Torre, Derek S Welsbie, Yang Sun, Xin Duan, Jeffrey Louis Goldberg, Marcus Braun, Zdenek Lansky, Yang Hu.

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTNΔC) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C- terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

DOI: https://doi.org/10.1101/2024.04.02.587832
Transl Neurodegener. 2024 Apr 17. 13(1): 23

Focusing on mitochondria in the brain: from biology to therapeutics.

Nanshan Song, Shuyuan Mei, Xiangxu Wang, Gang Hu, Ming Lu.

  Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to the physiology and pathology of many organs and tissues, among which the brain is particularly prominent. The brain demands 20% of the resting metabolic rate and holds highly active mitochondrial activities. Considerable research shows that mitochondria are closely related to brain function, while mitochondrial defects induce or exacerbate pathology in the brain. In this review, we provide comprehensive research advances of mitochondrial biology involved in brain functions, as well as the mitochondria-dependent cellular events in brain physiology and pathology. Furthermore, various perspectives are explored to better identify the mitochondrial roles in neurological diseases and the neurophenotypes of mitochondrial diseases. Finally, mitochondrial therapies are discussed. Mitochondrial-targeting therapeutics are showing great potentials in the treatment of brain diseases.

Keywords:  Brain; Mitochondria; Mitochondrial transfer; Neurological disorders

DOI:  https://doi.org/10.1186/s40035-024-00409-w
Int J Med Sci. 2024 ;21(5): 809-816

Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.

Tianen Wang, Guoli Xing, Tong Fu, Yanchun Ma, Qi Wang, Shuxiang Zhang, Xing Chang, Ying Tong.

  This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Keywords:  cardiotoxicity; doxorubicin; mitochondria; mitochondrial quality control

DOI:  https://doi.org/10.7150/ijms.94485
Mol Aspects Med. 2024 Apr 15. pii: S0098-2997(24)00031-1. [Epub ahead of print]97 101272

Delineating the contribution of ageing and physical activity to changes in mitochondrial characteristics across the lifespan.

Matthew J-C Lee, Nicholas J Saner, Alessandra Ferri, Esther García-Domínguez, James R Broatch, David J Bishop.

Ageing is associated with widespread physiological changes prominent within all tissues, including skeletal muscle and the brain, which lead to a decline in physical function. To tackle the growing health and economic burdens associated with an ageing population, the concept of healthy ageing has become a major research priority. Changes in skeletal muscle mitochondrial characteristics have been suggested to make an important contribution to the reductions in skeletal muscle function with age, and age-related changes in mitochondrial content, respiratory function, morphology, and mitochondrial DNA have previously been reported. However, not all studies report changes in mitochondrial characteristics with ageing, and there is increasing evidence to suggest that physical activity (or inactivity) throughout life is a confounding factor when interpreting age-associated changes. Given that physical activity is a potent stimulus for inducing beneficial adaptations to mitochondrial characteristics, delineating the influence of physical activity on the changes in skeletal muscle that occur with age is complicated. This review aims to summarise our current understanding and knowledge gaps regarding age-related changes to mitochondrial characteristics within skeletal muscle, as well as to provide some novel insights into brain mitochondria, and to propose avenues of future research and targeted interventions. Furthermore, where possible, we incorporate discussions of the modifying effects of physical activity, exercise, and training status, to purported age-related changes in mitochondrial characteristics.

DOI: https://doi.org/10.1016/j.mam.2024.101272
J Physiol. 2024 Apr 17.

Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.

Jerónimo Aragón-Vela, Rafael A Casuso, Ana Sagrera Aparisi, Julio Plaza-Díaz, Ascensión Rueda-Robles, Agustín Hidalgo-Gutiérrez, Luis Carlos López, Andrea Rodríguez-Carrillo, José Antonio Enriquez, Sara Cogliati, Jesús R Huertas.

  In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highly metabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletal muscle. Rats were randomly allocated into a normoxia control group (n = 10) and a hypoxia group (n = 30), divided into three groups (0, 6, and 24 h post-MHH). The normoxia situation was recapitulated at the University of Granada, at 662 m above sea level. The MHH situation was performed at the High-Performance Altitude Training Centre of Sierra Nevada located in Granada at 2320 m above sea level. We found a significant increase in mitochondrial supercomplex assembly in the heart as soon as the animals reached 2320 m above sea level and their levels are maintained 24 h post-exposure, but not in skeletal muscle. Furthermore, in skeletal muscle, at 0 and 6 h, there was increased dynamin-related protein 1 (Drp1) expression and a significant reduction in Mitofusin 2. In conclusion, mitochondria from the muscle and heart respond differently to MHH: mitochondrial supercomplexes increase in the heart, whereas, in skeletal muscle, the mitochondrial pro-fission response is trigged. Considering that skeletal muscle was not actively involved in the ascent when the heart was beating faster to compensate for the hypobaric, hypoxic conditions, we speculate that the different responses to MHH are a result of the different energetic requirements of the tissues upon MHH. KEY POINTS: The heart and the skeletal muscle showed different mitochondrial responses to moderate hypobaric hypoxia. Moderate hypobaric hypoxia increases the assembly of the electron transport chain complexes into supercomplexes in the heart. Skeletal muscle shows an early mitochondrial pro-fission response following exposure to moderate hypobaric hypoxia.

Keywords:  heart; mitochondria; moderate hypobaric hypoxia; skeletal muscle; supercomplexes

DOI:  https://doi.org/10.1113/JP285516
Nat Aging. 2024 Apr 16.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Xiaorui Chen, Yang Luo, Qing Zhu, Jingzi Zhang, Huan Huang, Yansheng Kan, Dian Li, Ming Xu, Shuohan Liu, Jianxiao Li, Jinmeng Pan, Li Zhang, Yan Guo, Binghao Wang, Guantong Qi, Zhen Zhou, Chen-Yu Zhang, Lei Fang, Yanbo Wang, Xi Chen.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

DOI: https://doi.org/10.1038/s43587-024-00612-4
Int J Physiol Pathophysiol Pharmacol. 2024 ;16(1): 1-9

Extracellular vesicles and their therapeutic applications: a review article (part1).

Diana Rafieezadeh, Aryan Rafieezadeh.

Extracellular vesicles (EVs) have emerged as a captivating field of study in molecular biology with diverse applications in therapeutics. These small membrane-bound structures, released by cells into the extracellular space, play a vital role in intercellular communication and hold immense potential for advancing medical treatments. EVs, including exosomes, microvesicles, and apoptotic bodies, are classified based on size and biogenesis pathways, with exosomes being the most extensively studied. The aim of this study was to examine the molecular secretory pathway of exosomes and to discuss the medical applications of exosomes and the methods for employing them in laboratory models. The therapeutic potential of EVs has garnered significant attention. Their unique properties, such as stability, biocompatibility, and capacity to traverse biological barriers, make them promising vehicles for targeted drug delivery. By engineering EVs to carry specific cargo molecules, such as therapeutic proteins, small interfering Ribonucleic Acid (RNAs) (siRNAs), or anti-cancer drugs, researchers can enhance drug stability and improve their targeted delivery to specific cells or tissues. This approach has the potential to minimize off-target effects and increase therapeutic efficacy, offering a more precise and effective treatment strategy. EVs represent a captivating and rapidly evolving field with significant therapeutic implications. Their role in intercellular communication, targeted drug delivery, and regenerative medicine makes them valuable tools for advancing medical treatments. As our understanding of EV biology and their therapeutic applications continues to expand, we can expect remarkable advancements that will revolutionize the field of medicine and lead to more personalized and effective therapies.

Keywords: Extracellular vehicles (EVs); intercellular communication; regenerative medicine; stem cells; targeted drug delivery; therapeutic proteins
Mol Biol Rep. 2024 Apr 16. 51(1): 522

Human umbilical cord mesenchymal stem cell-derived exosomes alleviate the severity of experimental autoimmune encephalomyelitis and enhance lag-3 expression on foxp3 + CD4 + T cells.

Adel Mohammadzadeh, Masoud Lahouty, Hamed Charkhian, Arash Adamnejad Ghafour, Sahand Moazzendizaji, Jafar Rezaei, Shahriar Alipour, Vahid Shafiei Irannejad, Mohammad Hassan Khadem Ansari.

   BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Understanding the dysregulation of Tregs, dynamic cells involved in autoimmunity, is crucial in comprehending diseases like MS. However, the role of lymphocyte-activation gene 3 (Lag-3) in MS remains unclear.
METHODS: In this study, we explore the potential of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSCs-Exs) as an immune modulator in experimental autoimmune encephalomyelitis (EAE), a model for MS.
RESULTS: Using flow cytometry, our research findings indicate that groups receiving treatment with hUMSC-Exs revealed a significant increase in Lag-3 expression on Foxp3 + CD4 + T cells. Furthermore, cell proliferation conducted on spleen tissue samples from EAE mice using the CFSE method exposed to hUMSC-Exs yielded relevant results.
CONCLUSIONS: These results suggest that hUMSCs-Exs could be a promising anti-inflammatory agent to regulate T-cell responses in EAE and other autoimmune diseases. However, further research is necessary to fully understand the underlying mechanisms and Lag-3's precise role in these conditions.

Keywords:  EAE; Exosomes; HUMSCs; Lag-3 and tregs

DOI:  https://doi.org/10.1007/s11033-024-09433-5
Small. 2024 Apr 19. e2311071

The Role of Extracellular Vesicles in the Treatment of Prostate Cancer.

Cong Hu, Qi Chen, Tianyang Wu, Xinxing Du, Yanhao Dong, Zehong Peng, Wei Xue, Vijaya Sunkara, Yoon-Kyoung Cho, Liang Dong.

  Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.

Keywords:  extracellular vesicles; functional materials; nanomolecule; prostate cancer; therapeutic targets; treatment

DOI:  https://doi.org/10.1002/smll.202311071
Cell Death Discov. 2024 Apr 17. 10(1): 180

PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration.

Wenting You, Kèvin Knoops, Tos T J M Berendschot, Birke J Benedikter, Carroll A B Webers, Chris P M Reutelingsperger, Theo G M F Gorgels.

Neurodegenerative disorders are characterized by the progressive loss of structure and function of neurons, often including the death of the neuron. Previously, we reported that, by removing the cell death stimulus, dying/injured neurons could survive and recover from the process of regulated cell death, even if the cells already displayed various signs of cellular damage. Now we investigated the role of mitochondrial dynamics (fission/fusion, biogenesis, mitophagy) in both degeneration and in recovery of neuronal cells. In neuronal PC12 cells, exposure to ethanol (EtOH) induced massive neurite loss along with widespread mitochondrial fragmentation, mitochondrial membrane potential loss, reduced ATP production, and decreased total mitochondrial volume. By removing EtOH timely all these mitochondrial parameters recovered to normal levels. Meanwhile, cells regrew neurites and survived. Study of the mitochondrial dynamics showed that autophagy was activated only during the cellular degeneration phase (EtOH treatment) but not in the recovery phase (EtOH removed), and it was not dependent on the Parkin/PINK1 mediated mitophagy pathway. Protein expression of key regulators of mitochondrial fission, phospho-Drp1Ser616 and S-OPA1, increased during EtOH treatment and recovered to normal levels after removing EtOH. In addition, the critical role of PGC-1α mediated mitochondrial biogenesis in cellular recovery was revealed: inhibition of PGC-1α using SR-18292 after EtOH removal significantly impeded recovery of mitochondrial damage, regeneration of neurites, and cell survival in a concentration-dependent manner. Taken together, our study showed reversibility of mitochondrial morphological and functional damage in stressed neuronal cells and revealed that PGC-1α mediated mitochondrial biogenesis played a critical role in the cellular recovery. This molecular mechanism could be a target for neuroprotection and neurorescue in neurodegenerative diseases.

DOI: https://doi.org/10.1038/s41420-024-01953-0
Inflammation. 2024 Apr 16.

Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.

Jun Tong, Genhong Yao, Yueqin Chen, Hairong Xie, Xinyu Zheng, Lingyun Sun, Zhenping Huang, Zhenggao Xie.

  Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

Keywords:  Diabetic retinopathy; HMGB1/TLR4; Inflammation; Mesenchymal stem cells; Microglial polarization

DOI:  https://doi.org/10.1007/s10753-024-02005-6
Age Ageing. 2024 Apr 01. pii: afae079. [Epub ahead of print]53(4):

Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.

Qu Tian, Erin E Greig, Keenan A Walker, Kenneth W Fishbein, Richard G Spencer, Susan M Resnick, Luigi Ferrucci.

   BACKGROUND: Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function.
METHODS: We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4 years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black).
RESULTS: The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures.
CONCLUSION: Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes.

Keywords:  cognition; metabolomics; mitochondria; motor; older people; skeletal muscle

DOI:  https://doi.org/10.1093/ageing/afae079
Lupus. 2024 Apr 15. 9612033241247622

Extracellular mitochondrial components as new biomarkers for lupus nephritis.

Sharath Gowda, Khushboo Rana, Ankit Kumar, Pradip Kumar Prajapati, Namisha Patel, Sapan Pandya, Ratika Srivastava.

  Major reason for mortality among systemic lupus erythematosus patients is renal failure due to the deposition of immune complexes in the glomeruli. Being a chronic disease with multiple relapses and remissions across the lifespan, it's important to know the degree of nephritis for diagnosis as well as the long-term clinical management of the patients. Currently, renal biopsy is being used as the gold standard to diagnose and define the stages of the disease. However, renal biopsy being invasive only provides a localized picture of nephritis, and has the risk of bleeding. Additionally, it is also cost-intensive. Hence, a reliable, non-invasive biomarker is required for lupus nephritis. This study has evaluated extracellular mitochondrial components, including cell-free mitochondria, and cell-free mitochondrial DNA as probable biomarkers of the degree of nephritis. Both showed a significant correlation with proteinuria and protein-creatinine ratio. Our study substantiates their usage as clinical biomarkers of nephritis upon their validation in a larger cohort of lupus nephritis patients and other forms of nephritis. Although the current data suggest using cell-free mitochondria as a biomarker of lupus nephritis is better than the cell-free mitochondrial DNA.

Keywords:  Systemic lupus erythematosus; biomarker; cell-free mitochondria; cell-free mitochondrial DNA; lupus nephritis

DOI:  https://doi.org/10.1177/09612033241247622
Am J Physiol Lung Cell Mol Physiol. 2024 Apr 16.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Qinglan He, Peijun Li, Lihua Han, Chen Yang, Meiling Jiang, Yingqi Wang, Xiaoyu Han, Yuanyuan Cao, Xiaodan Liu, Weibing Wu.

  Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Keywords:  airway epithelial dysfunction; chronic obstructive pulmonary disease; mechanisms; mitochondrial

DOI:  https://doi.org/10.1152/ajplung.00362.2023