bims-nenemi 2025-01-05 papers

bims-nenemi

Biomed News

on Neuroinflammation, neurodegeneration and mitochondria

Issue of 2025–01–05
twelve papers selected by
Marco Tigano, Thomas Jefferson University

Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.
Mitochondria-Nucleus Migration Probe for Ultrasensitive Monitoring of mtDNA Damage in Living Cells.
Flow-cytometry reveals mitochondrial DNA accumulation in Saccharomyces cerevisiae cells during cell cycle arrest.
Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity.
Lipotoxicity-induced upregulation of FIS1 exacerbates mitochondrial fragmentation and promotes NLRP3-dependent pyroptosis in diabetic cardiomyopathy.
Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.
D-loop mutations in mitochondrial DNA are a risk factor for chemotherapy resistance in esophageal cancer.
Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.
Oxidative stress mediates retinal damage after corneal alkali burn through the activation of the cGAS/STING pathway.
Global organelle profiling reveals subcellular localization and remodeling at proteome scale.
PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.
GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression.

Sci Adv. 2025 Jan 03. 11(1): eads8489

Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.

Xiujie Li-Harms, Jingjun Lu, Yu Fukuda, John Lynch, Aditya Sheth, Gautam Pareek, Marcin M Kaminski, Hailey S Ross, Christopher W Wright, Amber L Smith, Huiyun Wu, Yong-Dong Wang, Marc Valentine, Geoffrey Neale, Peter Vogel, Stanley Pounds, John D Schuetz, Min Ni, Mondira Kundu.

The role of somatic mitochondrial DNA (mtDNA) mutations in leukemogenesis remains poorly characterized. To determine the impact of somatic mtDNA mutations on this process, we assessed the leukemogenic potential of hematopoietic progenitor cells (HPCs) from mtDNA mutator mice (Polg D257A) with or without NMyc overexpression. We observed a higher incidence of spontaneous leukemogenesis in recipients transplanted with heterozygous Polg HPCs and a lower incidence of NMyc-driven leukemia in those with homozygous Polg HPCs compared to controls. Although mtDNA mutations in heterozygous and homozygous HPCs caused similar baseline impairments in mitochondrial function, only heterozygous HPCs responded to and supported altered metabolic demands associated with NMyc overexpression. Homozygous HPCs showed altered glucose utilization with pyruvate dehydrogenase inhibition due to increased phosphorylation, exacerbated by NMyc overexpression. The impaired growth of NMyc-expressing homozygous HPCs was partially rescued by inhibiting pyruvate dehydrogenase kinase, highlighting a relationship between mtDNA mutation burden and metabolic plasticity in leukemogenesis.

DOI: https://doi.org/10.1126/sciadv.ads8489
Anal Chem. 2024 Dec 31.

Mitochondria-Nucleus Migration Probe for Ultrasensitive Monitoring of mtDNA Damage in Living Cells.

Zhen-Qing Yu, Wenjing Pan, Xiaofeng Yang, Minggang Tian, Jing Zhang, Hongwen Liu, Lei Yang, Xingjiang Liu, Mei Yan, Shuai Xu.

Mitochondrial DNA (mtDNA) damage is a prevalent phenomenon that has been proven to be implicated in a wide spectrum of diseases. However, the progressive attenuation of probe signals in response to mtDNA damage within living cells inherently limits the sensitivity and precision of current probes for detecting mtDNA damage. Herein, we employ an innovative organelle signal ratio imaging approach, utilizing the mitochondria-nucleus migration probe MCQ, to achieve unparalleled sensitivity in detecting mtDNA damage in living cells. MCQ exhibited an initial preferential binding to mtDNA, facilitated by its cationic quinolinium moiety, but migrated to the nucleus upon mtDNA damage. This unique migration behavior not only enhanced the spatial identifiability of mtDNA damage but also amplified detection sensitivity and precision significantly by harnessing the intensified nucleus signal against the attenuated mitochondrial signal. This innovative approach established a positive correlation between the signal and mtDNA damage, enabling the detection of even subtle mtDNA damage at the early stage of apoptosis with a remarkable 23-fold enhancement following just 5 min H2O2 induction in living cells, whereas conventional methods relying solely on the fading of mitochondrial signals proved insufficient. Furthermore, MCQ's ability to monitor the occurrence of mtDNA damage achieved the intricate differentiation between apoptosis and ferroptosis. By monitoring mtDNA damage, drug-induced apoptosis in cancer cells was further conducted using MCQ to evaluate the therapeutic efficacy of four anticancer drugs at very low concentrations. This innovative strategy not only paves the way for ultrasensitive detection of mtDNA damage but also holds immense promise for early monitoring of mtDNA damage-associated diseases.

DOI: https://doi.org/10.1021/acs.analchem.4c04862
Front Cell Dev Biol. 2024 ;12 1497652

Flow-cytometry reveals mitochondrial DNA accumulation in Saccharomyces cerevisiae cells during cell cycle arrest.

Elena Yu Potapenko, Nataliia D Kashko, Dmitry A Knorre.

  Mitochondria are semi-autonomous organelles containing their own DNA (mtDNA), which is replicated independently of nuclear DNA (nDNA). While cell cycle arrest halts nDNA replication, mtDNA replication continues. In Saccharomyces cerevisiae, flow cytometry enables semi-quantitative estimation of mtDNA levels by measuring the difference in signals between cells lacking mtDNA and those containing mtDNA. In this study, we used flow cytometry to investigate mtDNA accumulation in yeast cells under G1 and G2 phase cell cycle arrest conditions utilising thermosensitive mutants cdc4-3 and cdc15-2. In line with the previous studies, cell cycle arrest induced a several-fold accumulation of mtDNA in both mutants. The total DNA levels in arrested cells correlated with cell forward scattering, suggesting a relationship between individual cell mtDNA quantity and size. In cell cycle-arrested cells, we observed no correlation between cell size and intercellular mtDNA copy number variability. This implies that as cell size increases during arrest, the mtDNA content remains within a specific limited range for each size class. This observation suggests that mtDNA quantity control mechanisms can function in cell cycle-arrested cells.

Keywords:  cell cycle arrest; cell cycle defect; mtDNA; mtDNA copy number; mtDNA copy number control; yeast

DOI:  https://doi.org/10.3389/fcell.2024.1497652
Anal Chem. 2025 Jan 01.

Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity.

Lanlan Chen, Jingjing Lai, Siqi Dong, Wenjun Liu, Ximei Zhang, Huanghao Yang.

Evaluating tumor radiosensitivity is beneficial for the prediction of treatment efficacy, customization of treatment plans, and minimization of side effects. Tracking the mitochondrial DNA (mtDNA) repair process helps to assess tumor radiosensitivity as mtDNA repair determines the fate of the cell under radiation-induced mtDNA damage. However, current probes developed to monitor levels of DNA repair enzymes suffered from complex synthesis, uncontrollable preparation, limited tumor selectivity, and poor organelle-targeting ability. Especially, the correlation between mtDNA repair activity and inherent radiosensitivity of tumors has not yet been explored. Here, we present a mitochondria-targeted DNA-based nanoprobe (TPP-Apt-tFNA) for in situ monitoring of the activity of the mtDNA repair enzyme and evaluating tumor radiosensitivity. TPP-Apt-tFNA consists of a DNA tetrahedral framework precisely modified with three functional modules on each of the three vertexes, that is, the tumor cell-targeting aptamer, the mitochondrion-targeting moiety, and the apurinic/apyrimidinic endonuclease 1 (APE1)-responsive molecule beacon. Once selectively internalized by tumor cells, the nanoprobe targeted the mitochondrion and specifically recognized APE1 to activate fluorescence, allowing the observation of mtDNA repair activity. The nanoprobe showed elevated APE1 levels in the mitochondria of tumor cells under oxidative stress. Moreover, the nanoprobe enabled the illumination of different levels of APE1-mediated mtDNA repair activity in different cell cycle phases. Furthermore, using the nanoprobe in vitro and in vivo, we found that tumor cells with high activity of mtDNA repair, which allowed them to recover from radiation-induced mtDNA lesions, had low sensitivity to radiation and an unsatisfactory radiotherapy outcome. Our work provides a new imaging tool for exploring the roles of mtDNA repair activity in diverse biological processes and for guiding tumor radiation treatment.

DOI: https://doi.org/10.1021/acs.analchem.4c04408
Free Radic Biol Med. 2024 Dec 27. pii: S0891-5849(24)01158-4. [Epub ahead of print]

Lipotoxicity-induced upregulation of FIS1 exacerbates mitochondrial fragmentation and promotes NLRP3-dependent pyroptosis in diabetic cardiomyopathy.

Libo Luo, Qingrui Wu, Qingyu Xiao, Yuqiong Chen, Zhanxiang Deng, Chunren Cen, Jijin Lin.

   BACKGROUND: Lipotoxicity is a significant factor in the pathogenesis of diabetic cardiomyopathy (DbCM), a condition characterized by mitochondrial fragmentation and pyroptosis. Mitochondrial fission protein 1 (FIS1) plays a role in mitochondrial fission by anchoring dynamin-related protein 1 (DRP1). However, the specific contribution of FIS1 to DbCM remains unclear. This study aims to clarify how lipotoxicity-induced upregulation of FIS1 affects mitochondrial fragmentation and the mechanisms linking this fragmentation to NLRP3-dependent pyroptosis in DbCM.
METHODS: To model lipotoxicity in DbCM, we used db/db mice and primary neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA) and conducted a series of in vivo and in vitro experiments. Gain- and loss-of-function studies on NRCMs were performed using pharmacological inhibitors and small interfering RNA (siRNA) transfection, and we assessed the expression and function of FIS1, mitochondrial dynamics, mitochondrial reactive oxygen species (mitoROS) production, NLRP3-dependent pyroptosis, and their interrelationships.
RESULTS: Our results show that in the myocardium of db/db mice, NLRP3-dependent pyroptosis is associated with upregulation of FIS1, mitochondrial fragmentation, and increased oxidative stress. In NRCMs subjected to PA, the application of VX-765 and MCC950 to inhibit caspase-1 and NLRP3, respectively, significantly reduced pyroptosis. Additionally, pretreatment with Mito-TEMPO (MT) demonstrated that mitoROS are critical initiators for NLRP3 inflammasome activation and subsequent pyroptosis. Furthermore, PA-induced upregulation of FIS1 exacerbates mitochondrial fragmentation. Downregulation of FIS1 or inhibition of FIS1/DRP1 interaction reversed mitochondrial fragmentation, reduced mitoROS levels, and mitigated pyroptosis.
CONCLUSIONS: Lipotoxicity-induced FIS1 upregulation exacerbates mitochondrial fragmentation through its interaction with DRP1, leading to increased mitoROS production and the initiation of NLRP3-dependent pyroptosis in DbCM. Therefore, targeting FIS1 emerges as a potential therapeutic approach for managing DbCM.

Keywords:  Diabetic cardiomyopathy; FIS1; Inflammation; Lipotoxicity; Mitochondrial fragmentation; Pyroptosis; mitoROS

DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.12.049
Nat Microbiol. 2025 Jan 02.

Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.

Xueliang Wang, Yi Fang, Wei Liang, Yuhong Cai, Chi Chun Wong, Junlin Wang, Na Wang, Harry Cheuk-Hay Lau, Ying Jiao, Xingyu Zhou, Liufang Ye, Mengmiao Mo, Tao Yang, Miao Fan, Lei Song, Heming Zhou, Qiang Zhao, Eagle Siu-Hong Chu, Meinong Liang, Weixin Liu, Xin Liu, Shuaiyin Zhang, Haitao Shang, Hong Wei, Xiaoxing Li, Lixia Xu, Bing Liao, Joseph J Y Sung, Ming Kuang, Jun Yu.

Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis.

DOI: https://doi.org/10.1038/s41564-024-01890-9
Sci Rep. 2024 Dec 30. 14(1): 31653

D-loop mutations in mitochondrial DNA are a risk factor for chemotherapy resistance in esophageal cancer.

Takashi Harino, Koji Tanaka, Daisuke Motooka, Yasunori Masuike, Tsuyoshi Takahashi, Kotaro Yamashita, Takuro Saito, Kazuyoshi Yamamoto, Tomoki Makino, Yukinori Kurokawa, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki.

  Esophageal cancer is a highly aggressive disease, and acquired resistance to chemotherapy remains a significant hurdle in its treatment. mtDNA, crucial for cellular energy production, is prone to mutations at a higher rate than nuclear DNA. These mutations can accumulate and disrupt cellular function; however, mtDNA mutations induced by chemotherapy in esophageal cancer remain unexplored. We aimed to identify such mutations in esophageal cancer, pre- and post-chemotherapy, and explore the relationship between them and clinicopathological factors associated with chemotherapy resistance. We investigated mtDNA mutations in Human esophageal squamous cell carcinoma (ESCC) cancer cell lines (TE8 and TE11) and patient samples (27 pre- and post-chemotherapy, and 96 post-chemotherapy) using next-generation sequencing. Our analysis revealed a rise in mtDNA mutations following chemotherapy, particularly within the D-loop region. Moreover, mutations in a specific D-loop segment (hypervariable segment 1; HVS1) were associated with lower mtDNA copy number, poorer response to chemotherapy, and decreased five-year survival rates. These findings suggest that HVS1 mutations in mtDNA acquired after chemotherapy may contribute to treatment resistance and poorer clinical outcomes in patients with esophageal cancer. This study sheds light on the mechanisms of chemotherapy resistance and provides valuable insights for future research to overcome this challenge.

Keywords:  Chemotherapy; D-loop; Esophageal cancer; Mitochondrial DNA; MtDNA copy number; Mutation

DOI:  https://doi.org/10.1038/s41598-024-80226-3
Signal Transduct Target Ther. 2024 Dec 30. 9(1): 367

Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.

Yu-Jia-Nan Chen, Rong-Chen Shi, Yuan-Cai Xiang, Li Fan, Hong Tang, Gang He, Mei Zhou, Xin-Zhe Feng, Jin-Dong Tan, Pan Huang, Xiao Ye, Kun Zhao, Wen-Yu Fu, Liu-Li Li, Xu-Ting Bian, Huan Chen, Feng Wang, Teng Wang, Chen-Ke Zhang, Bing-Hua Zhou, Wan Chen, Tao-Tao Liang, Jing-Tong Lv, Xia Kang, You-Xing Shi, Ellen Kim, Yin-Hua Qin, Aubryanna Hettinghouse, Kai-di Wang, Xiang-Li Zhao, Ming-Yu Yang, Yu-Zhen Tang, Hai-Long Piao, Lin Guo, Chuan-Ju Liu, Hong-Ming Miao, Kang-Lai Tang.

Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages. Here, we found that L-malate exerts anti-inflammatory effect via BiP-IRF2BP2 signaling, which is a sensor of cytosolic pH in macrophages. First, L-malate, a TCA intermediate upregulated in pro-inflammatory macrophages, was identified as a potent anti-inflammatory metabolite through initial screening. Subsequent screening with DARTS and MS led to the isolation of L-malate-BiP binding. Further screening through protein‒protein interaction microarrays identified a L-malate-restrained coupling of BiP with IRF2BP2, a known anti-inflammatory protein. Interestingly, pH reduction, which promotes carboxyl protonation of L-malate, facilitates L-malate and carboxylate analogues such as succinate to bind BiP, and disrupt BiP-IRF2BP2 interaction in a carboxyl-dependent manner. Both L-malate and acidification inhibit BiP-IRF2BP2 interaction, and protect IRF2BP2 from BiP-driven degradation in macrophages. Furthermore, both in vitro and in vivo, BiP-IRF2BP2 signal is required for effects of both L-malate and pH on inflammatory responses. These findings reveal a previously unrecognized, proton/carboxylate dual sensing pathway wherein pH and L-malate regulate inflammatory responses, indicating the role of certain carboxylate metabolites as adaptors in the proton biosensing by interactions between macromolecules.

DOI: https://doi.org/10.1038/s41392-024-02076-9
Exp Eye Res. 2024 Dec 28. pii: S0014-4835(24)00450-0. [Epub ahead of print] 110228

Oxidative stress mediates retinal damage after corneal alkali burn through the activation of the cGAS/STING pathway.

Keli Mao, Yanqiao Huang, Zheng Liu, Wenjun Sui, Chong Liu, Yujie Li, Jieting Zeng, Xiaobing Qian, Xinqi Ma, Xiaofeng Lin, Bingsheng Lou.

Retinal damage accounts for irreversible vision loss following ocular alkali burn (OAB), but the underlying mechanisms remain largely unexplored. Herein, using an OAB mouse model, we examined the impact of oxidative stress (OS) in retinal damage and its molecular mechanism. Results revealed that OS in the retina was enhanced soon after alkali injury. Antioxidant therapy with N-acetylcysteine (NAC) preserved the retinal structure, suppressed cell apoptosis and decreased retinal inflammation, confirming the role of OS. Moreover, enhanced OS was linked to mitochondrial dysfunction, mtDNA leakage and initiation of the cytosolic DNA-sensing signaling. The activation of the major DNA sensors cyclic GMP-AMP Synthase (cGas) and cGAS-Stimulator of Interferon Genes (cGAS/STING) pathway was then identified. Notably, inhibiting cGAS/STING signaling with C-176 markedly reduced inflammation and cell apoptosis and ultimately protected the retina against OAB. Overall, our study reveals the vital function of OS in the occurence of OAB-induced retinal damage and the involvement of cGAS/STING activation. Furthermore, our provides preclinical validation of the use of an antioxidant or a STING inhibitor as a potential therapeutic approach to protect the retina after OAB.

DOI: https://doi.org/10.1016/j.exer.2024.110228
Cell. 2024 Dec 26. pii: S0092-8674(24)01344-8. [Epub ahead of print]

Global organelle profiling reveals subcellular localization and remodeling at proteome scale.

Marco Y Hein, Duo Peng, Verina Todorova, Frank McCarthy, Kibeom Kim, Chad Liu, Laura Savy, Camille Januel, Rodrigo Baltazar-Nunez, Madhurya Sekhar, Shivanshi Vaid, Sophie Bax, Madhuri Vangipuram, James Burgess, Leila Njoya, Eileen Wang, Ivan E Ivanov, Janie R Byrum, Soorya Pradeep, Carlos G Gonzalez, Yttria Aniseia, Joseph S Creery, Aidan H McMorrow, Sara Sunshine, Serena Yeung-Levy, Brian C DeFelice, Shalin B Mehta, Daniel N Itzhak, Joshua E Elias, Manuel D Leonetti.

  Defining the subcellular distribution of all human proteins and their remodeling across cellular states remains a central goal in cell biology. Here, we present a high-resolution strategy to map subcellular organization using organelle immunocapture coupled to mass spectrometry. We apply this workflow to a cell-wide collection of membranous and membraneless compartments. A graph-based analysis assigns the subcellular localization of over 7,600 proteins, defines spatial networks, and uncovers interconnections between cellular compartments. Our approach can be deployed to comprehensively profile proteome remodeling during cellular perturbation. By characterizing the cellular landscape following HCoV-OC43 viral infection, we discover that many proteins are regulated by changes in their spatial distribution rather than by changes in abundance. Our results establish that proteome-wide analysis of subcellular remodeling provides key insights for elucidating cellular responses, uncovering an essential role for ferroptosis in OC43 infection. Our dataset can be explored at organelles.czbiohub.org.

Keywords:  CRISPR; HCoV-OC43 coronavirus; cell biology; ferroptosis; k-NN graph; mass spectrometry; native organelle IP; protein localization; spatial proteomics; subcellular remodeling; viral infection

DOI:  https://doi.org/10.1016/j.cell.2024.11.028
Nat Commun. 2025 Jan 02. 16(1): 256

PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.

Marion Haas, Sabrina Cherfa, Léa Nguyen, Maxence Bourgoin, Gersende Caron, Elise Dessauge, Tony Marchand, Laurent Delpy, Patrick Auberger, Jérôme Moreaux, Arnaud Jacquel, Thierry Fest.

Our study explores the complex dynamics of the integrated stress response (ISR) axis, highlighting PIM2 kinase's critical role and its interaction with the BCL2 protein family, uncovering key mechanisms of cell survival and tumor progression. Elevated PIM2 expression, a marker of various cancers, often correlates with disease aggressiveness. Using a model of normal and malignant plasma cells, we show that inhibiting PIM2 kinase inhibits phosphorylated BAD production and activates ISR-mediated NOXA expression. This shift towards MCL1 dependence underscores the synergy achieved through combined PIM/MCL1 inhibition, driven largely by ISR-mediated NOXA expression. In mouse xenograft models, dual targeting of PIM2 and MCL1 effectively controls tumor growth-a response reversed by ISR-specific inhibition and upregulation of genes linked to tumor cell dissemination. This work elucidates the molecular intricacies of PIM2 inhibition and its implications for cancer therapy, especially in tumors with elevated PIM2 expression.

DOI: https://doi.org/10.1038/s41467-024-55572-5
Nat Commun. 2024 Dec 30. 15(1): 10923

GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression.

Kai Shen, Hao Zhou, Qiang Zuo, Yue Gu, Jiangqi Cheng, Kai Yan, Huiwen Zhang, Huanghe Song, Wenwei Liang, Jinchun Zhou, Jiuxiang Liu, Feng Liu, Chenjun Zhai, Weimin Fan.

Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression. Here, we elucidate a positive correlation between fibroblast-like synoviocyte senescence and osteoarthritis progression and reveal that GATD3A deficiency induces fibroblast-like synoviocyte senescence. Mechanistically, GATD3A deficiency enhances the binding of Sirt3 to MDH2, leading to deacetylation and decreased activity of MDH2. Reduced MDH2 activity impairs tricarboxylic acid cycle flux, resulting in mitochondrial dysfunction and fibroblast-like synoviocyte senescence. Intra-articular injection of recombinant adeno-associated virus carrying GATD3A significantly alleviates the osteoarthritis phenotype in male mice. This study increases our current understanding of GATD3A function. In particular, we reveal a novel mechanism of fibroblast-like synoviocyte senescence, suggesting that targeting GATD3A is a potential therapeutic approach for osteoarthritis.

DOI: https://doi.org/10.1038/s41467-024-55335-2