{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies on the Ups/PRELI family of lipid transfer proteins have elucidated the molecular determinants that govern lipid specificity across the mitochondrial intermembrane space. Structural analyses and molecular dynamics simulations have revealed that PRELID3B, in complex with TRIAP1, is uniquely configured to shuttle phosphatidylserine rather than other phospholipids. Key amino acids involved in head group recognition and the hydrophobic properties of flexible loops together regulate the entry of lipids into its binding cavity, while differential membrane orientations during lipid release further highlight its specialized role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, functional genomics and pan-cancer analyses have identified the same protein, known also as SLMO2, as a vital lipid transporter in the context of cancer biology. SLMO2/PRELID3B has been found to facilitate the transport of phosphatidylserine into the mitochondrial interior, and its dysregulated overexpression is correlated with enhanced cell proliferation, migration, and poorer overall prognosis across various tumor types. This oncogenic role is further supported by observed mutation patterns, differential promoter methylation, and a positive association with myeloid-derived suppressor cell (MDSC) immune infiltration, underscoring its potential as both a prognostic biomarker and a therapeutic target in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings emphasize the dual functional importance of PRELID3B: it is critical not only for maintaining mitochondrial lipid homeostasis through precise phospholipid transfer but also for modulating oncogenic processes when aberrantly expressed. The integrative insights from structural biology and cancer genomics suggest that targeting PRELID3B could have significant therapeutic implications, potentially allowing for modulation of mitochondrial lipid profiles and tumor microenvironment dynamics concurrently."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xeni Miliara, Takashi Tatsuta, Jamie-Lee Berry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-09089-x"}], "href": "https://doi.org/10.1038/s41467-019-09089-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30850607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30850607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiong Liu, Renming Yuan, Jie Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLMO2 is a potential prognostic and immunological biomarker in human pan-cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-51720-5"}], "href": "https://doi.org/10.1038/s41598-024-51720-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38212657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38212657"}]}]}]}