bims-miptne 2025-06-08 papers

J Physiol. 2025 May 31.

Mitochondrial oxidative stress, calcium and dynamics in cardiac ischaemia-reperfusion injury.

Emily Rozich, Ulas Ozkurede, Shanmugasundaram Pakkiriswami, Ryan Gemilere, Samira M Azarin, Julia C Liu.

Ischaemia-reperfusion injury (IRI) is a major cause of cardiomyocyte damage and death from myocardial infarction. Oxidative stress, dysregulated calcium (Ca2+) handling and disrupted mitochondrial dynamics are all key factors in IRI and can play a role in cell death. Mitochondria are a primary source of oxidative stress, which is generated by electron leak from the respiratory chain complexes and the oxidation of accumulated succinate upon reperfusion. The mitochondrial permeability transition pore (mPTP), a high conductance channel that forms following reperfusion of ischaemic mitochondria, has been implicated in reperfusion-induced cell death. Although factors including mitochondrial Ca2+ overload and oxidative stress that regulate mPTP opening have been well characterized, the composition of the mPTP is still actively investigated. Clinically, mPTP opening and IRI complicate treatment of myocardial infarction. Therefore, many possible therapeutics to reduce the damaging effects of reperfusion are under investigation. Antioxidants, pharmaceutical approaches, postconditioning and synthetic polymers have all been investigated for use in IRI. Still, many of these therapeutics of interest have shown mixed evidence underlying their use in preclinical and clinical research. In this review we discuss our current understanding of the contributions of mitochondrial oxidative stress, mitochondrial Ca2+ and mitochondrial dynamics to cardiomyocyte damage and death in IRI, and where further clarification of these mechanisms is needed to identify potential therapeutic targets.

Keywords: calcium; ischaemia–reperfusion injury; mitochondria; mitochondrial dynamics; myocardial infarction; oxidative stress

DOI: https://doi.org/10.1113/JP287770

J Lipid Res. 2025 May 29. pii: S0022-2275(25)00094-X. [Epub ahead of print] 100834

Mitochondrial Calcium Uniporter is Required for Thermogenic Adaptation Mediated by Reactive Oxygen Species Signaling.

Suji Kim, Seung-Kuy Cha, Kyu-Sang Park, Jun Namkung.

Mitochondrial Ca2+ influx via mitochondrial calcium uniporter (MCU) accelerates mitochondrial biogenesis and energy metabolism. Nevertheless, the molecular mechanism of MCU-dependent mitochondrial activation and thermogenesis in thermogenic adipose tissues remains elusive. In this study, we demonstrate that MCU governs mitochondrial functions in brown and beige adipocytes via the formation of mitochondrial reactive oxygen species (mtROS). Mice with a brown adipose tissue-specific Mcu knockout (Mcu BKO) mice exhibited decreased oxygen consumption and heat production, accompanied by downregulation of genes related to β-oxidation and thermogenesis. Furthermore, Mcu BKO mice, exhibiting a reduction in mtROS, showed defective thermogenic responses to cold exposure or β-adrenergic stimulation. Downregulation of thermogenic genes including Ucp1 in Mcu BKO mice can be rescued by exogenous ROS through AMP-activated protein kinase (AMPK) activation. Collectively, our results suggest that MCU modulates mtROS formation, which in turn mediates mitonuclear signaling to cellular response with mitochondrial activation.

Keywords: Adipocytes; Adipose tissue; Lipolysis and fatty acid metabolism; Mitochondria; Obesity; brown

DOI: https://doi.org/10.1016/j.jlr.2025.100834

Trends Cancer. 2025 Jun 03. pii: S2405-8033(25)00126-8. [Epub ahead of print]

The extracellular matrix in cancer: from understanding to targeting.

Jessica L Chitty, Thomas R Cox.

Significant advances in matrix biology research have enhanced our understanding of individual matrix components and extracellular matrix (ECM) signalling. The dysregulation of the ECM during the development of solid tumours is a critical area of investigation. Despite recent progress, further investigation into the role of the ECM in cancer progression and therapeutic targeting remains essential for improving outcomes. This study is especially relevant for ECM-rich cancers, such as pancreatic cancer, which is characterised by dense fibrosis that impacts all stages of tumour development, including initiation, progression, and chemoresistance. Currently, no matrix-targeting agents have achieved mainstream clinical implementation. Challenges in this field include insufficient integration of new technologies, and limited understanding of cross disciplinary influences and of the complex, multifunctional nature of the ECM. In this review, we highlight key areas of matrix biology research that are crucial for advancing cancer treatment.

Keywords: extracellular matrix; pancreatic cancer; stroma; tumour microenvironment

DOI: https://doi.org/10.1016/j.trecan.2025.05.003