Acyl-CoA–binding protein (ACBP, encoded by diazepam binding inhibitor, DBI) is an abundant intracellular regulator of lipid metabolism that also circulates systemically, yet the mechanisms governing its release and its relationship to organ injury remain unresolved. Herein, we combine human multi-omics, mechanistic mouse models and controlled cell death assays to identify cell...
Despite advances in the treatment of metastatic colorectal cancer (mCRC), it remains the second leading cause of cancer-related mortality, with limited effective therapeutic options. While EGFR inhibition is a standard first-line therapy for mCRC patients lacking KRAS mutations, resistance frequently develops, limiting its clinical benefit. Murine CRC models have shown that EGFR...
Mitochondrial Ca2+ uptake shapes cellular signaling by modulating metabolism, cell death and cytosolic Ca2+ dynamics, yet its pathological and therapeutic relevance remains undefined. Here, we show that Ca2+ entry through the mitochondrial Ca2+ uniporter (MCU) is required for mitochondrial fragmentation and subsequent NLRP3 inflammasome-mediated IL-1β release in...
Oncogene-induced senescence (OIS), a cellular programme initiated by activation of oncogenic signalling, provides a barrier to transformation and is accompanied by major reprogramming of cellular metabolism. We show here that induction of OIS by BRAFV600E expression in human diploid fibroblasts led to global changes in the cellular lipidome, characterised by a strong increase in...
Spermatogenesis requires precise spatial and temporal regulation of RNA splicing, orchestrated by both the major (U1, U2, and U4/U6/U5) and minor (U11, U12, and U4atac/U6atac/U5) spliceosomal small nuclear ribonucleoproteins (snRNPs), yet their function during germ cell development remain poorly defined. Here, we elucidate the essential function of LSM7, a component of the LSM2-8...
Chemotherapy remains a cornerstone therapeutic approach for gastric cancer (GC). However, the clinical efficacy of docetaxel is substantially limited by the emergence of drug resistance. Here, we discovered a novel DDR1/VEGFR2 inhibitor, K-13, and further confirmed its selectivity by comprehensive kinase profiling in vitro. Through screening of K-13 in combination with...
The BCL2-like protein MCL1 plays pivotal roles in apoptosis and non-apoptotic functions. While many BCL2 family members are predicted to be tail-anchored (TA) proteins, direct evidence for MCL1’s membrane targeting via the GET pathway, a major pathway for membrane insertion of TA proteins, has been lacking. Using degron-mediated depletion of GET3 (ASNA1/TRC40) in human cell lines...
The transition of embryonic stem cells (ESCs) from a pluripotent state to lineage commitment is governed by complex regulatory mechanisms, including chromatin remodeling, as well as transcriptional and post-transcriptional processes. Recent studies have emphasized the interplay between these mechanisms, revealing intricate, multilayered regulatory networks that require further...
The progression of acute kidney injury (AKI) to chronic kidney disease (CKD) remains a major clinical challenge. It is primarily triggered by renal tubular epithelial cell (RTEC) death that leads to persistent sterile inflammation, maladaptive repair and irreversible renal fibrosis. A pivotal event in RTEC death is plasma membrane rupture (PMR), which leads to the release of...
Ferroptosis represents an iron-dependent form of cell death characterized by accumulation of lipid peroxides. However, it is largely elusive how authentic lipid metabolites contribute to ferroptosis, and whether this is dysregulated in malignant cells due to metabolic rewiring. Here, we identify fatty acid amide hydrolase (FAAH) as a crucial ferroptosis regulator in lung...
Prostate cancer (PCa) is a biologically heterogeneous disease that frequently progresses to castration-resistant prostate cancer (CRPC), a challenging clinical stage. The underlying mechanisms driving CRPC progression and resistance to androgen receptor (AR) signaling inhibition (ARSI) remain incompletely understood. Emerging evidence implicates the canonical Wnt pathway as a key...
Ubiquitination is a versatile post-translational modification that regulates protein stability, localisation and signalling. By modifying a wide range of substrates, ubiquitination controls key physiological processes, including inflammatory responses, which are the focus of this article. Precise regulation of inflammatory signalling is essential, as insufficient activation...
An interplay of growth factors and signaling pathways governs the development and maintenance of lymphatic vasculature, ensuring proper fluid homeostasis and immune function. Disruption of these regulatory mechanisms can lead to congenital lymphatic disorders and contribute to various pathological conditions. However, the mechanisms underlying the molecular regulation of these...
Huntington’s disease (HD) is an incurable, neurodegenerative disorder. While the causative mutation – CAG expansions within the coding region of the Huntingtin (HTT) gene – has been identified over 30 years ago, the pathological mechanisms underlying HD are still not clear. The abnormal CAG track encodes a polyglutamine (polyQ) expanded protein, which leads to HTT protein...
Peroxisomes are dynamic organelles essential for lipid metabolism, oxidative balance, and cellular stress responses. Their dysfunction contributes to various diseases, including metabolic and neurodegenerative disorders. Selective autophagy, or pexophagy, preserves peroxisomal quality by removing damaged or excess peroxisomes. Here, we propose a novel ATM-PINK1-STUB1-ABCD3-SQSTM1...
Stress granules (SGs) are dynamic, membraneless ribonucleoprotein condensates that assemble in response to cellular stress and coordinate diverse cellular stress responses and diseases. Although SG have been reported to associate with the endoplasmic reticulum (ER), how ER-localized stress granule assembly is organized and regulated remains unclear. STING (stimulator of...
Histone methylation plays a critical role in chromatin accessibility and transcription regulation, with implications for various disorders, including osteoporosis. Jumonji C domain-containing protein 7 (JMJD7) demethylates arginine (R) residues on histones, influencing tissue metabolism and integrity. However, its role in bone tissue remains uncharacterized. We have discovered...