Lipid droplet-mitochondria contact sites are important membrane contact sites that connect lipid storage, fatty acid oxidation, and mitochondrial homeostasis. As the liver is responsible for lipid synthesis, storage, oxidation, and export, it provides an ideal setting for investigating the roles of these contact sites in physiological adaptation and pathological remodeling. Growing evidence suggests that, both in chronic lipid overload-induced hepatic metabolic injury and in acute hepatic ischemia-reperfusion injury, lipid droplet-mitochondria contact sites are positioned at the intersection of lipid flux regulation, mitochondrial stress thresholds, and inflammatory injury amplification. During the early stage of metabolic stress, moderate lipid droplet formation and lipid droplet-mitochondrial coupling may facilitate lipid sequestration, fatty acid partitioning, and energy adaptation. However, under persistent lipid burden or reperfusion-associated oxidative stress, a mismatch between lipid droplet mobilization and mitochondrial uptake/oxidative capacity may lead to amplified lipotoxicity, reactive oxygen species bursts, mitochondrial DNA leakage, and sterile inflammation. In recent years, advances in super-resolution imaging, proximity labeling and spatial proteomics have promoted a shift in this field from morphological colocalization studies toward closed-loop analysis of structure, composition, and function. This review summarizes the structural basis and functional heterogeneity of lipid droplet-mitochondria contact sites, as well as their roles in hepatic metabolic injury and ischemia-reperfusion injury, and discusses their translational potential as disease stratification markers and therapeutic targets.

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.