Mitochondrial dynamics in health and disease: mechanisms and potential targets

Abstract Mitochondria are organelles that are able to adjust and respond to different stressors and metabolic needs within a cell, showcasing their plasticity and dynamic nature. These abilities allow them to effectively coordinate various cellular functions. Mitochondrial dynamics refers to the changing process of fission, fusion, mitophagy and transport, which is crucial for optimal function in signal transduction and metabolism. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular fate, and a range of diseases, including neurodegenerative disorders, metabolic diseases, cardiovascular diseases and cancers. Herein, we review the mechanism of mitochondrial dynamics, and its impacts on cellular function. We also delve into the changes that occur in mitochondrial dynamics during health and disease, and offer novel perspectives on how to target the modulation of mitochondrial dynamics

Editorial : Macrophage immunity and metabolism in cancer: Novel diagnostic and therapeutic strategies

Non peer reviewe

Two spectrophotometric methods for the determination of azithromycin and roxithromycin in pharmaceutical preparations

Two new and simple spectrophotometric procedures have been proposed and validated for estimation of two important macrolide antibiotics namely, azithromycin dihydrate and roxithromycin. Method I depends on complex formation between any of the two drugs and copper in acidic medium where the absorbances of the produced complexes are measured at 250 and 264 nm with linearity ranges of 1.0-100.0 and 2.0-130.0 µg/mL for the two drugs, respectively. Method II depends on the reaction of these drugs with N-bromosuccinimide forming a product which is yellow colored, measured at 264 and 278 nm, with linearity ranges of 2.0-140.0 and 3.0-160.0 µg/mL for azithromycin dihydrate and roxithromycin, respectively. The proposed methods were subjected to detailed validation procedure; moreover they were used for the estimation of the concerned drugs in their different dosage forms. Study of the reactions stoichiometry was carried out; furthermore, a reaction mechanism proposal was presented

Stromal interaction molecule 1/microtubule‐associated protein 1A/1B‐light chain 3B complex induces metastasis of hepatocellular carcinoma by promoting autophagy

Abstract Metastasis is the leading cause of death in hepatocellular carcinoma (HCC) patients, and autophagy plays a crucial role in this process by orchestrating epithelial–mesenchymal transition (EMT). Stromal interaction molecule 1 (STIM1), a central regulator of store‐operated calcium entry (SOCE) in nonexcitable cells, is involved in the development and spread of HCC. However, the impact of STIM1 on autophagy regulation during HCC metastasis remains unclear. Here, we demonstrate that STIM1 is temporally regulated during autophagy‐induced EMT in HCC cells, and knocking out (KO) STIM1 significantly reduces both autophagy and EMT. Interestingly, STIM1 enhances autophagy through both SOCE‐dependent and independent pathways. Mechanistically, STIM1 directly interacts with microtubule‐associated protein 1A/1B‐light chain 3B (LC3B) to form a complex via the sterile‐α motif (SAM) domain, which promotes autophagosome formation. Furthermore, deletion of the SAM domain of STIM1 abolishes its binding with LC3B, leading to a decrease in autophagy and EMT in HCC cells. These findings unveil a novel mechanism by which the STIM1/LC3B complex mediates autophagy and EMT in HCC cells, highlighting a potential target for preventing HCC metastasis

Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma

Abstract Background The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. Methods A high throughput liquid chromatography‐tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment‐resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient‐derived organoid (PDO) assays. Results A multiomics profiling of 8536 high‐confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment‐resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5‐lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. Conclusion Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC