Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)

Published: Nov. 26, 2024

Abstract Regulated cell death (RCD) refers to the form of that can be regulated by various biomacromolecules. Each modalities have their distinct morphological changes and molecular mechanisms. However, intense evidences suggest lipid peroxidation common feature initiates propagates death. Excessive alters property membrane further damage proteins nucleic acids, which is implicated in human pathologies. Here, we firstly review classical chain process peroxidation, clarify current understanding myriad roles mechanisms RCD types. We also discuss how involves diseases such intimate association between peroxidation-driven leveraged develop rational therapeutic strategies.

Language: Английский

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Machine learning with label-free Raman microscopy to investigate ferroptosis in comparison with apoptosis and necroptosis

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 11, 2025

Human and animal health rely on balancing cell division death to maintain normal homeostasis. This process is accomplished by regulated (RCD), whose imbalance can lead disease. Currently, the most frequently used method for analyzing RCD fluorescence microscopy. has limitations potential side effects due presence of fluorescent labels. Furthermore, often lacks specificity may have effects. In quest overcome such difficulties, label-free approaches come into focus.Here, Raman microscopy in combination with machine learning investigate RCDs, where biochemical molecular "fingerprints" are investigated a focus vibrations atoms molecules. Three different unique types genetic machinery, namely, ferroptosis studied comparison apoptosis, necroptosis murine fibroblast line L929sAhFas. Interestingly, during ferroptosis, decrease wavenumber at 939 cm-1 was observed, which associated reduction expression collagen – compound essential multiple diseases. Data analysis performed (ML), here SVMs, model utilizing spectra directly support vector (SVM) outperforms other SVM strategies correctly predicting 73% all spectra. Other methods: PCA-SVM (principal component analysis-SVM), peak fitting-AUC-SVM (area under curve) fitting-spectral reconstruction-SVM rendered prediction accuracies ~52%, ~43%, 61%, respectively. Peak fitting additional benefit enabling biological interpretation scattering peaks using area curve, although loss general accuracy. The biology, pipelines, be applied broader field not limited death. Verduijn et al show that modalities. allows investigation apoptosis necroptosis.

Language: Английский

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Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 25, 2025

Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism membrane function. Evidence for cross-talk between these is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids become susceptible peroxidation under additional stress. This reprogramming altered acyl-CoA synthetase isoenzyme expression caused by a decrease in growth factor receptor tyrosine kinase (RTK)-phosphatidylinositol-3-kinase signaling, resulting suppressed acid biosynthesis, specific stressors impaired Akt-SREBP1 activation. The reduced availability of de novo synthesized favors the channeling phospholipids. Growth withdrawal serum starvation mimics this phenotype, whereas RTK ligands counteract it. We conclude attenuated signaling during cell initiation increases cells’ susceptibility oxidative damage at interface alternative programs.

Language: Английский

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The Mechanisms and Implications of Cardiolipin in the Regulation of Cell Death

Cell Biochemistry and Function, Journal Year: 2025, Volume and Issue: 43(3)

Published: March 1, 2025

ABSTRACT Cardiolipin (CL), an exclusive phospholipid, is predominantly found within the confines of inner mitochondrial membrane, playing indispensable role in sustenance operations and regulation cellular energy metabolism. The influence CL on pathways cell death has garnered significant interest recent scholarly discourse. This review delves into multifaceted roles across various modes demise, encompassing apoptosis, autophagy, pyroptosis, ferroptosis, necrosis, necroptosis. discussion extends to examination CL's implications a clinical context, particularly concerning cardiovascular maladies, neurological degeneration, oncological conditions. Through integrative analysis contemporary research findings, aim elucidate intricate dynamics involvement phenomena. While acknowledging inherent limitations hurdles faced by current endeavors, therapeutic potential as modulator nonetheless encouraging. Forthcoming investigations must surmount these obstacles, thereby uncovering nuanced mechanisms impacts realm associated pathologies, potentially paving way for innovative intervention strategies.

Language: Английский

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Characterization and differentiation of myocardial remodeling using artificial intelligence‐assisted confocal Raman spectroscopy imaging

View, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Myocardial remodeling is a crucial pathophysiological factor underlying heart failure, the leading cause of death globally. In this study, we utilized confocal Raman spectroscopy imaging to gain unprecedented insights into myocardial tissue during remodeling. We induced in rats via subcutaneous administration isoproterenol (ISO) (5 mg/kg) over seven days, meticulously validated by echocardiography and histopathological staining. Subsequent analyses using transmission electron microscopy revealed significant mitochondrial damage. Confocal imaging, however, provided most detailed visualization complex architecture within remodeled tissue. Notably, technique enabled precise differentiation between hypertrophic fibrotic regions myocardium. These findings not only deepen our understanding mechanisms driving but also highlight transformative potential as label‐free, high‐resolution tool for assessing cardiac pathology. Additionally, artificial intelligence (AI) assisted identification rapid sites tissues further enhance technology targeted clinical applications, marking advancement managing failure.

Language: Английский

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In Situ Surface-Enhanced Raman Spectroscopy for Membrane Protein Analysis and Sensing

Biosensors and Bioelectronics, Journal Year: 2024, Volume and Issue: 267, P. 116819 - 116819

Published: Sept. 30, 2024

Language: Английский

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