bims-miptne 2025-07-13 papers

Science. 2025 Jul 10. 389(6756): 157-162

ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox.

Maintenance of mitochondrial redox homeostasis is of fundamental importance to cellular health. Mitochondria harbor a host of intrinsic antioxidant defenses, but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood. We found a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through contact-mediated reactive oxygen species (ROS) transfer. We found that ACBD5 and PTPIP51 form a contact between peroxisomes and mitochondria. The percentage of these contacts increased during mitochondrial oxidative stress and helped to maintain mitochondrial health through the transfer of mitochondrial ROS to the peroxisome lumen. Our findings reveal a multiorganelle layer of mitochondrial antioxidant defense-suggesting a direct mechanism by which peroxisomes contribute to mitochondrial health-and broaden the scope of known membrane contact site functions.

DOI: https://doi.org/10.1126/science.adn2804

Mol Aspects Med. 2025 Jul 07. pii: S0098-2997(25)00046-9. [Epub ahead of print]104 101382

Ischemia - Reperfusion injury: A roadmap to precision therapies.

Wei Li, Yan Liao, Jie Chen, Weichao Kang, Xintao Wang, Xiaozhu Zhai, Ying Xue, Wangzheqi Zhang, Yiyang Xia, Derong Cui.

Ischemia-reperfusion (I/R) injury is prevalent in the medical field and significantly limits the therapeutic outcomes of various ischemic diseases, adversely affecting patient prognosis. The pathogenesis of I/R injury is highly complex, involving intricate interactions among oxidative stress, inflammatory responses, mitochondrial dysfunction, and multiple cell death pathways. Once the mitochondrial respiratory chain is impaired, it triggers oxidative stress responses, leading to the excessive production of reactive oxygen species (ROS). Excessive ROS not only directly damage cells but also activate inflammatory responses and initiate multiple cell death signalling pathways, such as necroptosis, pyroptosis, and ferroptosis, thereby exacerbating tissue damage. Moreover, the clinical manifestations of I/R injury vary significantly across different organs, such as the heart, brain, kidneys, liver, and lungs, and are further influenced by patients' underlying conditions, posing challenges for clinical diagnosis and treatment. Therefore, constructing a comprehensive assessment system based on individual patient characteristics (such as genetic polymorphisms and comorbidities) to accurately predict the risk of I/R injury is particularly important. Currently, there are diverse strategies for the prevention and treatment of I/R injury, but translating basic research into clinical application remains challenging. Developing personalized treatment plans tailored to different cell types holds promise for overcoming existing therapeutic bottlenecks, significantly improving patient outcomes, and providing new directions for addressing the challenges of I/R injury.

Keywords: Cell death; I/R injury; Inflammatory factor; Ischemia-reperfusion injury; Molecular mechanisms

DOI: https://doi.org/10.1016/j.mam.2025.101382

Int J Biochem Cell Biol. 2025 Jul 03. pii: S1357-2725(25)00095-0. [Epub ahead of print]186 106827

Mitochondrial homeostasis and their impact on gastric carcinoma.

Amrutha Arjunan, Ganesh Venkatraman, Leena Dennis Joseph, Lakshmi R Perumalsamy.

Gastric cancer is the fifth most diagnosed cancer and the third most common cause of cancer-related deaths worldwide. Mitochondrial dysfunction, with its impaired energy production and increased oxidative stress, fuels the development of gastric tumours. Gastric cancer exhibits dysregulated mitochondrial functions, which contribute to metabolic reprogramming, decreased apoptosis sensitivity, therapeutic resistance, and enhanced tumour progression and metastasis. In addition, aberrations in mitochondrial DNA, respiratory chain complexes, and epigenetic alterations foster a pro-tumorigenic microenvironment. Although significant progress has been made in understanding the various molecular mechanisms involved in gastric carcinogenesis, further studies are needed to elucidate mitochondrial homeostasis in gastric cancer. Unravelling mitochondrial intricacies in gastric cancer could open the development of definitive diagnostic and therapeutic interventions driving tumour growth. This review focuses on investigating the altered mitochondrial functionalities in gastric cancer.

Keywords: Gastric cancer; Helicobacter pylori; Metabolic homeostasis; Mitochondria; Mitochondria-targeted drug therapy; MtDNA mutations

DOI: https://doi.org/10.1016/j.biocel.2025.106827

Sci Adv. 2025 Jul 11. 11(28): eadu5915

Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.

John Heath, Ryuhjin Ahn, Valerie Sabourin, Young Kyuen Im, Sabrina Rezzara Richard, Alva Annett, Caitlynn Mirabelli, Samantha Worme, Sarah M Maritan, Caitlyn Mourcos, Anna Maria Lazaratos, Elias Maldonado, Yun Yun Shen, Forest M White, Claudia L Kleinman, Peter M Siegel, Josie Ursini-Siegel.

Although effective for immunologically hot tumors, immune checkpoint inhibitors minimally affect tumors that are not T cell inflamed, including breast cancer. An alternate strategy to combat immune cold breast tumors may be to reeducate innate immunity. This study identifies strategies to skew neutrophils to acquire tumoricidal properties. Systemic Toll-like receptor (TLR)-induced inflammation, concomitant with mitochondrial complex I inhibition in breast tumors, increases neutrophil cytotoxicity against breast cancer cells and independently of CD8+ T cell immunity. These therapy-entrained neutrophils enhance secretory granule production, increasing expression of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase machinery and inducing a respiratory burst. Moreover, systemic administration of TLR agonists elevates nuclear factor κB signaling in neutrophils to increase production of secretory granule and NADPH oxidase machinery components, whereas complex I inhibitors are required to potentiate oxidative damage. In summary, we describe a class of neutrophils, educated by the combined action of inflammatory mediators and metabolic inhibitors, having tumoricidal functions.

DOI: https://doi.org/10.1126/sciadv.adu5915