bims-miptne 2025-11-23 papers

bims-miptne

Biomed News

on Mitochondrial permeability transition pore-dependent necrosis

Issue of 2025–11–23
eleven papers selected by
Oluwatobi Samuel Adegbite, University of Liverpool

Hydrostatic pressure induces mitochondrial oxidative stress and mtDNA-mediated cGAS-STING activation in acute pancreatitis.
Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma.
Complex II inhibition suppresses RSL3-induced ferroptosis by restoring mitochondrial bioenergetics.
Targeting the Powerhouse: A Critical Review of Mitochondrial Inhibitors as a Therapeutic Strategy in Lung Cancer.
Quantitative phosphoproteomic-based insights into dephosphorylation-enhanced myofibrillar protein degradation via mitochondrial apoptosis modulation.
Novel Allogeneic Mitochondria and Associated Organelle Complex Treatment Prevents Myocardial Ischemia-Reperfusion Injury Through Anti-Apoptotic Effects.
Ppif Gene KO Alleviates Pancreatic Injury in Mice With Cecal Ligation and Puncture-induced Sepsis.
Constructing a novel MPT-driven necrosis-associated gene set for predicting prognosis and immune status in skin cutaneous melanoma.
Cell death forms in myocardial ischemia-reperfusion injury and their potential clinical applications.
Succinate Dehydrogenase-Deficient Cancer Cells Have Increased Susceptibility to Ym155 Induced DNA Damage.
A Decade of Mitochondria-Targeting Drugs in Cancer Treatment: Case Review on Mitochondria-Targeting Curcumin or Mitocurcumin.

Free Radic Biol Med. 2025 Nov 17. pii: S0891-5849(25)01376-0. [Epub ahead of print]243 126-142

Hydrostatic pressure induces mitochondrial oxidative stress and mtDNA-mediated cGAS-STING activation in acute pancreatitis.

Fan Chen, Kedong Xu, Yimin Han, Jiachun Ding, Jiaqiang Ren, Weikun Qian, Zheng Wang, Zheng Wu, Zhenhua Ma, Fang Cao.

  Increased mechanical pressure is a well-recognized feature of acute pancreatitis (AP), but its pathological mechanisms remain elusive. Although previous studies have emphasized shear stress-induced pancreatic injury, the effects of static hydrostatic pressure have been underappreciated. Mitochondria act as mechanosensitive organelles, and mechanical stimuli can induce mitochondrial oxidative stress. Release of mitochondrial DNA (mtDNA) could trigger activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in immune cells. However, whether increased hydrostatic pressure can induce mtDNA-mediated cGAS-STING activation in pancreatic cells is unknown. In this study, we explored the mechanistic links between pressure-induced mitochondrial dysfunction, mtDNA release, and innate immune signaling activation in AP. Acute pancreatitis was induced in mice using two models: (1) intraperitoneal injection of caerulein combined with lipopolysaccharide (LPS), and (2) retrograde infusion of methylene blue-balanced salt solution through the pancreatic duct followed by briefly clamping to mimic elevated intrapancreatic hydrostatic pressure. AR42J cells, an immortalized pancreatic adenocarcinoma cell line exhibiting acinar-like characteristics, were cultured under controlled high hydrostatic pressure conditions to investigate pressure-induced cellular responses in vitro. Elevated hydrostatic pressure markedly aggravated mitochondrial dysfunction and induced mitochondrial permeability transition pore (MPTP) opening, accompanied by increased mitochondrial ROS production, leading to mtDNA leakage and cGAS-STING pathway activation, which exacerbated inflammatory responses and AP. Inhibition of MPTP suppressed mtDNA release, reduced STING activation, and ameliorated pancreatic injury. Collectively, our data show that increased hydrostatic pressure is a critical but underappreciated mechanical insult that causes mitochondrial dysfunction and mtDNA release in pancreatic cells through MPTP opening. The associated increase in mitochondrial oxidative stress may represent a key upstream trigger in this process, and cytosolic mtDNA could subsequently activate cGAS-STING signaling and exacerbate inflammatory responses in AP. These findings suggest that mitochondrial permeability transition is a potential therapeutic target in pressure-associated AP.

Keywords:  Acinar cell injury; Acute pancreatitis; Hydrostatic pressure; Mitochondrial DNA; cGAS–STING pathway

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.11.031
Sci Rep. 2025 Nov 19. 15(1): 40875

Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma.

Yikai Wang, Dingyang Lv, Wei Zhang, Weibing Shuang.

  Mitochondrial permeability transition (MPT)-driven necrosis is associated with kidney renal clear cell carcinoma (KIRC), but its role in prognosis remains unclear. This study develops a prognostic model for KIRC outcomes using MPT-driven necrosis-related genes (MPTDNRGs). Differentially expressed genes (DEGs) from TCGA-KIRC samples were analyzed and categorized based on MPTDNRGs scores. Three key genes-IL2RA, CD7, and CXCL13-were identified as significant prognostic markers and used to construct a risk model, validated through public datasets and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The risk score and age were the independent prognostic factors. A nomogram incorporating these factors demonstrated good clinical utility. The high-risk group was enriched in immune-related pathways, such as systemic lupus erythematosus, while the low-risk group showed enrichment in metabolism-related pathways, including butanoate metabolism. Significant differences in 25 immune cells were observed between the risk groups, with the high-risk group exhibiting higher TIDE scores, suggesting a greater likelihood of immune escape. Additionally, a ceRNA network revealed complex interactions, such as CXCL13-hsa-miR-670-5p-AL121985.1, and predicted 25 transcription factors for key MPTDNRGs. This study presents a novel prognostic model for KIRC based on three MPTDNRGs, offering valuable insights into KIRC prognosis and potential therapeutic targets.

Keywords:  Competitive endogenous RNA; Driven necrosis; Enrichment analysis; MPT; Renal cell carcinoma

DOI:  https://doi.org/10.1038/s41598-025-24779-x
Biochem Biophys Res Commun. 2025 Nov 14. pii: S0006-291X(25)01686-9. [Epub ahead of print]792 152970

Complex II inhibition suppresses RSL3-induced ferroptosis by restoring mitochondrial bioenergetics.

Sun Chul Lee, Soo Kyung Lee, Hyun Kim, Kyu-Sang Park.

  The mitochondrial electron transport chain (ETC) serves as the main site of cellular energy production and a major source of reactive oxygen species (ROS) generation, which can contribute to the lipid peroxidation associated with ferroptosis. However, the critical roles of mitochondria in ferroptosis are still being debated, and the consequences for cell survival vary depending on different ferroptosis inducers or mitochondrial modulators. In the neuroblastoma clonal cells SH-SY5Y, we demonstrated that inhibition of mitochondrial Complex II by 2-thenoyltrifluoroacetone (TTFA) markedly suppressed RSL3-induced ferroptotic lipid peroxidation and cell death. RSL3, a known inhibitor of glutathione peroxidase 4 (GPX4), significantly increased the mitochondrial membrane potential and superoxide production while reducing ATP-linked oxygen consumption. Co-treatment with TTFA effectively attenuated RSL3-induced mitochondrial hyperpolarization, lowered mitochondrial ROS generation, and restored respiratory activities - particularly enhanced ATP-linked oxygen consumption and reduced proton leak. Consistently, TTFA restored ATP production suppressed by RSL3. In contrast, inhibition of Complex I by rotenone did not suppress superoxide production and lipid peroxidation induced by RSL3, although it provided some protection against RSL3-mediated cytotoxicity. These findings suggest that inhibition of Complex II confers protection against ferroptosis by maintaining mitochondrial redox balance and protecting mitochondrial energy metabolism. In addition, our results uncover a novel mitochondrial mechanism underlying RSL3-induced oxidative stress and ferroptosis that can be modulated through targeted regulation of the ETC.

Keywords:  2-thenoyltrifluoroacetone; ATP-linked respiration; Ferroptosis; Mitochondrial electron transport chain; Mitochondrial superoxide; RSL3

DOI:  https://doi.org/10.1016/j.bbrc.2025.152970
Eur J Pharmacol. 2025 Nov 18. pii: S0014-2999(25)01136-7. [Epub ahead of print] 178382

Targeting the Powerhouse: A Critical Review of Mitochondrial Inhibitors as a Therapeutic Strategy in Lung Cancer.

Woo Hyun Park.

  Lung cancer therapy is constrained by profound intrinsic and acquired resistance to targeted therapies and immunotherapy. To overcome this, a new therapeutic paradigm is emerging that targets the unique metabolic and survival dependencies of cancer cells. Mitochondria, the central hubs of metabolism, cell death, and signaling, represent a critical vulnerability. This review provides a new conceptual framework for understanding and targeting mitochondrial pathways in lung cancer. First, this review outlines the key "mitochondrial hallmarks" of lung cancer that create therapeutic windows, emphasizing the critical role of metabolic heterogeneity. Second, it provides a novel, mechanism-based classification of mitochondrial inhibitors into four major classes: (1) electron transport chain (ETC) inhibitors, (2) metabolic enzyme modulators, (3) apoptosis pathway modulators, and (4) mitochondrial quality control (MQC) disruptors. Third, this review critically analyzes the molecular mechanisms by which these inhibitors activate regulated cell death pathways (apoptosis, ferroptosis) and, most importantly, their potential in overcoming therapeutic resistance to standard-of-care. Fourth, it explores the mechanisms of mitochondrial crosstalk within the tumor microenvironment (TME), including intercellular transfer via tunneling nanotubes. Finally, this review presents a systematic review of the clinical landscape, synthesizing data from preclinical models and ongoing clinical trials. This review concludes by highlighting key limitations and future perspectives, positioning MQC and the mitochondrial unfolded protein response (UPRmt) as next-generation targets to improve patient outcomes.

Keywords:  Ferroptosis; Lung Cancer; Mitochondria; Mitochondrial Inhibitors; Mitochondrial Quality Control (MQC); Therapeutic Resistance

DOI:  https://doi.org/10.1016/j.ejphar.2025.178382
Food Chem. 2025 Nov 13. pii: S0308-8146(25)04356-0. [Epub ahead of print]497 147104

Quantitative phosphoproteomic-based insights into dephosphorylation-enhanced myofibrillar protein degradation via mitochondrial apoptosis modulation.

Qing Lei, Shunan Song, Yangyu Su, Wupeng Ge, Jiaying Zhang.

  This study aimed to elucidate the mechanism by which dephosphorylation accelerates myofibrillar protein degradation by regulating mitochondrial apoptosis in porcine postmortem muscle. Phosphoproteomic analysis revealed that mitochondrial proteins could be phosphorylated and dephosphorylated by PKA and AP, respectively, and these proteins are mainly involved in apoptotic signaling and cytoskeletal organization. Mitochondrial dysfunction, apoptosis, and myofibrillar degradation significantly increased from 2 h to 72 h postmortem, irrespective of phosphorylation status. Notably, the dephosphorylated group (AP) exhibited lower phosphorylation level but showed greater apoptotic potential and myofibrillar degradation, as evidenced by increased mitochondrial membrane permeability, cytochrome c oxidation, and marked reductions in desmin and troponin-T levels, which decreased by 49.3 % and 64.3 %, respectively-significantly exceeding those in the control and phosphorylated (PKA) groups. These findings suggest that dephosphorylation may enhance mitochondrial apoptotic signaling, which could accelerate postmortem degradation of myofibrillar proteins.

Keywords:  Fiber type; Microstructure; Mitochondrial apoptosis; Myofibrillar protein degradation; Protein phosphorylation

DOI:  https://doi.org/10.1016/j.foodchem.2025.147104
JACC Asia. 2025 Nov 12. pii: S2772-3747(25)00577-0. [Epub ahead of print]

Novel Allogeneic Mitochondria and Associated Organelle Complex Treatment Prevents Myocardial Ischemia-Reperfusion Injury Through Anti-Apoptotic Effects.

Takumi Hayashi, Yuuki Shimizu, Hisashi Ota, Keiichi Sakakibara, Haihang Luo, Takahiro Shibata, Yiyang Che, Tianyu Liu, Rei Shibata, Rick Tsai, Masashi Suganuma, Toyoaki Murohara.

   BACKGROUND: Ischemia-reperfusion (I/R) injury can damage mitochondria and lead to cardiomyocyte apoptosis. Freshly prepared autologous mitochondria have shown benefits against I/R injury, but it remains unclear whether allogeneic mitochondrial organelle complex Q (MRC-Q) after freeze-thawing can also be effective in this context.
OBJECTIVES: This study aimed to determine whether administering MRC-Q can protect the heart from ischemia I/R injury in animal models.
METHODS: The MRC-Q used in our current experiments was intactly isolated by proprietary technology and cryopreserved. A mouse and porcine model of cardiac I/R injury was employed. In vitro experiments were performed using H9C2 cardiomyocytes subjected to hypoxic-reoxygenation conditions.
RESULTS: Our initial study demonstrated that MRC-Q can be storable with a maintenance of adenosine triphosphate production capacity. Next, we tested cardioprotective effects of MRC-Q administration on I/R injury in a murine model. Compared to the vehicle group, the MRC-Q-treated group showed a reduction in infarct size with fewer apoptotic cells, a decrease in circulating cardiac enzymes, and an improvement in cardiac function. In vitro studies revealed that MRC-Q was taken up into cardiomyocyte cells in a time-dependent manner. Next, we demonstrated that cell viability was improved in the MRC-Q-treated group after hypoxia/reoxygenation. Further examinations suggested that one of the mechanisms of cardioprotection by MRC-Q could be mediated by the secretion of mitochondria-derived peptides, which could inhibit apoptosis-promoting signals. In addition, MRC-Q augmented endogenous mitochondrial quality control in injured myocytes followed by up-regulation of adenosine triphosphate production and anti-reactive oxygen species activity. Finally, a preclinical pig model also confirmed the cardioprotective effects of MRC-Q administration.
CONCLUSIONS: Our data demonstrated that freeze-thawed MRC-Q have a protective effect on the heart after I/R injury.

Keywords:  anti-apoptosis; cardioprotection; cryopreservation, ischemic reperfusion injury; mitochondria

DOI:  https://doi.org/10.1016/j.jacasi.2025.09.022
J Surg Res. 2025 Nov 20. pii: S0022-4804(25)00685-7. [Epub ahead of print]316 18-25

Ppif Gene KO Alleviates Pancreatic Injury in Mice With Cecal Ligation and Puncture-induced Sepsis.

Lijie Ma, Junjie Wang, Sheng Wang.

   INTRODUCTION: The peptidyl-propyl cis-trans isomerase F (Ppif) gene encodes cyclophilin D. Its involvement suggests that sepsis-induced pancreatic injury may relate to mitochondrial membrane pore transition proteins, offering potential targets for pancreatic functional protection. This study aimed to determine whether sepsis leads to pancreatic injury and whether knockout (KO) of Ppif protects against sepsis-induced pancreatic injury.
METHODS: A septic mouse model was established using cecal ligation and puncture (CLP). Mice were divided into four groups: sham, CLP, Ppif KO-sham, and Ppif KO-CLP. Serum amylase and interleukin (IL)-6 levels were measured in blood and pancreatic tissues 24 h post CLP. Pancreatic tissues were analyzed using hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and electron microscopy.
RESULTS: In the CLP-induced sepsis model mice, serum IL-6, serum amylase, pancreatic tissue pathological scores, and terminal deoxynucleotidyl transferase dUTP nick-end labeling apoptosis indices were elevated. Compared with wild-type CLP mice, Ppif KO mice exhibited lower levels of serum IL-6 and amylase, pancreatic tissue pathological scores, and apoptosis indices, indicating that KO of Ppif had a protective effect against septic pancreatic injury. Electron microscopy of tissues from CLP mice revealed basement membrane irregularities, nuclear shrinkage, mitochondrial swelling, cristae deformation, and endoplasmic reticulum structural disorder. In Ppif KO CLP mice, pancreatic acinar cells exhibited more autophagosomes.
CONCLUSIONS: Our study demonstrates that fecal peritonitis triggers a systemic inflammatory response, which subsequently induces pancreatic injury, and that KO of Ppif may mitigate this pathological injury.

Keywords:  Cyclophilin D; Pancreatic injury; Ppif gene; Sepsis

DOI:  https://doi.org/10.1016/j.jss.2025.10.020
J Cancer Res Clin Oncol. 2025 Nov 18. 151(12): 323

Constructing a novel MPT-driven necrosis-associated gene set for predicting prognosis and immune status in skin cutaneous melanoma.

Yang Wenxian, Fan Shuwen.

   BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive malignancy with limited prognostic markers. Mitochondrial permeability transition (MPT)-driven necrosis has been implicated in tumor progression and immune regulation, yet its role in SKCM remains unclear.
METHODS: 39 MPT-driven necrosis-related genes (MPTDNRG) were retrieved from Molecular Signatures Database (MSigDB). Using TCGA-SKCM and GTEx datasets, differentially expressed genes (DEGs) were identified and incorporated into Cox and LASSO analyses. An MPT-driven necrosis-related gene signature (MPTDNRGS) was constructed. The signature was validated in GEO cohorts (GSE19234, GSE65904). A nomogram integrating clinical factors was established to assess predictive performance. Functional enrichment, immune infiltration, and checkpoint responsiveness were evaluated. Single-cell RNA-seq (scRNA-seq) datasets were further analyzed to map cell-type-specific expression and T-cell trajectories.
RESULTS: A five gene signature (BIRC3, CASP7, ENDOG, PRF1, PRKCB) stratified patients into high and low risk groups with distinct survival outcomes. The nomogram achieved strong predictive accuracy (3-year AUC = 0.772). High risk patients exhibited suppressed immune activation, lower T-cell infiltration, and reduced predicted response to immune checkpoint inhibitors. Single cell analysis revealed higher MPTDNRGS scores in tumor-infiltrating T cells than in normal controls. Pseudotime trajectories showed cytotoxic T cells transitioning to immunosuppressive phenotypes, marked by progressive BIRC3 upregulation. Elevated BIRC3 correlated with immune inhibitory markers and enrichment of TGF-β and IL6/JAK/STAT3 pathways.
CONCLUSION: We established and validated a novel MPT-driven necrosis-based prognostic model for SKCM. This model reliably predicted patient outcomes and immune status. BIRC3 emerged as a potential regulator of T-cell dysfunction and a promising therapeutic target in SKCM.

Keywords:  Baculoviral IAP Repeat Containing 3 (BIRC3); MPT-driven necrosis-related gene signatures (MPTDNRGS); Mitochondrial permeability transition (MPT); Skin cutaneous melanoma (SKCM)

DOI:  https://doi.org/10.1007/s00432-025-06370-z
Mol Cell Biochem. 2025 Nov 18.

Cell death forms in myocardial ischemia-reperfusion injury and their potential clinical applications.

Yuantong Xu, Suying Wu, Lei Zhang, Menghe Zhang, Yonghao Jiang.

  Timely and effective reperfusion therapy is an effective means of relieving ischemic damage to cardiomyocytes and is also the most commonly used treatment for clinical ischemic heart disease. However, while reperfusion saves the ischemic myocardium, the explosive production of reactive oxygen species (ROS) and calcium overload can cause additional damage to cardiac tissue cells. This review describes the pathophysiological mechanisms of myocardial ischemia-reperfusion injury and the forms of myocardial tissue cell death mediated by the reperfusion process, including ferroptosis, pyroptosis, and necroptosis. We also report the latest research progress in treating myocardial reperfusion injury by targeting ferroptosis, pyroptosis, and necroptosis. The aim is to understand the mechanism of myocardial reperfusion injury better and provide new treatment ideas to reduce myocardial ischemia-reperfusion injury.

Keywords:  Ferroptosis; Ischemia-reperfusion injury; Lipid peroxidation; Mitochondria; Necroptosis; Targeted therapy

DOI:  https://doi.org/10.1007/s11010-025-05440-7
bioRxiv. 2025 Oct 01. pii: 2025.09.29.679343. [Epub ahead of print]

Succinate Dehydrogenase-Deficient Cancer Cells Have Increased Susceptibility to Ym155 Induced DNA Damage.

Qianjin Guo, Sooyeon Lee, Neali Armstrong, Brian Lim, Rebecca C Schugar, David Tomz, Haixia Xu, Anzel Zhen, Leor Needleman, Electron Kebebew, Justin P Annes.

The hereditary pheochromocytoma and paraganglioma (hPPGL) syndrome is caused by inherited mutations in Succinate Dehydrogenase genes (SDHx). Affected individuals are predisposed to developing pheochromocytomas (Pheo), paragangliomas (PGL), renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST). Notably, tumors with succinate dehydrogenase subunit B ( SDHB ) deficiency demonstrate increased metastatic risk, for which treatments remain palliative. Hence, discovering novel therapeutic avenues to improve the prognosis for SDHB -cancer patients is an urgent need. Here we employed human SDHB -deficient UOK269 RCC cells ( SDHB -KO) and isogenic SDHB -reconstituted control cells ( SDHB -WT) to discover SDH-dependent mitochondria-directed cytotoxic agents. Given the reduced ATP-generating capacity of SDHB -KO cells, we hypothesized they would be uniquely sensitive to futile cycle induction with mitochondrial ionophores (2,4-Dinitrophenol (2-DNP), BAM15, Niclosamide, Nitazoxanide). Indeed, these compounds exhibited preferential cytotoxicity toward SDHB -KO cells. However, the chemotherapeutic compound Ym155 demonstrated the most potent and dramatic (five-fold) preferential cytotoxicity towards SDHB -KO cells. Importantly, the SDH-dependent cytotoxicity of Ym155 was validated in both primary human pheochromocytoma cells and mouse pheochromocytoma (MPC) cells. Furthermore, because few SDH-deficient cell lines are available, we buttressed our findings in additional relevant cell lines by modeling SDH-deficiency using chemical SDH enzyme inhibition with 3-nitropropionic acid (3-NPA). We observed a persistent cooperativity between SDH-deficiency and Ym155 cytotoxicity across multiple cell lineages and disease models. Mechanistically, Ym155-induced cytotoxicity was independent of its primary target, Survivin. Instead, SDH-deficiency sensitized cells to Ym155-induced DNA damage. Strikingly, the phenotype of SDH-deficient Ym155 sensitivity was recapitulated by inhibition of the histone demethylase KDM4, a downstream consequence of SDH deficiency. Thus, the accumulation of succinate in SDH-deficient tumors inhibits KDM4 activity, impairs DNA repair and yields enhanced susceptibility to Ym155-induced reactive oxygen species (ROS) generation. The identified intrinsic susceptibilities of SDHB -deficient cancers has the potential to be therapeutically leveraged.

DOI: https://doi.org/10.1101/2025.09.29.679343
Drug Dev Res. 2025 Dec;86(8): e70188

A Decade of Mitochondria-Targeting Drugs in Cancer Treatment: Case Review on Mitochondria-Targeting Curcumin or Mitocurcumin.

Rahul Shah, Ryan Varghese, Harsh Anchan, Sanidhya Pai, Tanmay Zagade, Mitul Oswal, Sparsh Agarwal, Purab Sood, Gargi Digholkar, Abha Deshpande, Ravi Vamsi Peri, Pooja Tiwary, Krishil Oswal, Rohit Sharma.

  Mitochondrial targeting is of particular interest to researchers, as it presents as a personalized medicine approach in cancer cell metabolism and survival. By specifically targeting mitochondria, targeted therapies can disrupt energy production, induce apoptosis, and overcome drug resistance in cancer cells, potentially improving therapeutic outcomes. This review discusses the advancements in mitochondrial drug delivery over the last decade. It explores the potential of mitochondrial targeting using mitocurcumin (MTC), a novel small molecule curcumin analog that has been engineered to specifically target mitochondria in cancer cells, thereby augmenting its therapeutic efficacy. The antiproliferative activity of MTC demonstrates its ability to induce reactive oxygen species (ROS) production and promote oxidative stress-mediated apoptosis, oxidative damage, and cellular senescence in diverse cancer cell lines, thereby enhancing its specificity for cancer cells. Despite these encouraging attributes, current research on MTC remains limited. Further comprehensive investigations are imperative to fully elucidate the efficacy and potential applications of mitochondrial targeting, especially MTC, in oncological therapeutics, including in vivo efficacy trials, pharmacokinetic profiling, toxicology studies, and combination therapy assessments. Although mitochondrial targeting presents a promising avenue for cancer therapy, rigorous scientific inquiry is essential to validate its clinical potential and optimize its therapeutic application for improved patient compliance.

Keywords:  cellular senescence; chemical conjugation; mitochondrial‐targeting; mitocurcumin; oxidative stress; targeted cancer therapy

DOI:  https://doi.org/10.1002/ddr.70188