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Herein, a high\u2010efficiency long\u2010chain saturated fatty acid\u2010labeled sensor, termed HELLEN, based on the ligand binding domain (LBD) of peroxisome proliferator\u2010activated receptor alpha (PPAR\u03b1) and the \u201cLXXLL\u201d domain (LXD) of steroid receptor coactivator\u20101 (SRC\u20101) is generated via genetically encoded expression. HELLEN exhibits a pronounced fluorescent increase in response to intracellular stearic acid (SA, C18:0), one of the major LCSFAs, and this response demonstrates subcellular resolution and excellent selectivity. Using HELLEN, we detect the uptake of exogenous SA under physiological conditions and visualize SA translocation to mitochondria in hepatocytes under inflammatory stress. Furthermore, in an inflammatory mouse model, excessive LCSFAs, including SA, are trafficked to hepatic mitochondria. Together, HELLEN provides a novel tool for mapping SA metabolism and offers valuable insights into LCSFA\u2010related metabolic pathways.<\/jats:p>","DOI":"10.1002\/smtd.202502088","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:12:31Z","timestamp":1773133951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ligand\u2010Activated Fluorescent Probe Reveals Mitochondrial Long\u2010Chain Saturated Fatty Acid Flux: An Effective Tool for Metabolic Disorder Studies"],"prefix":"10.1002","volume":"10","author":[{"given":"Tianlan","family":"Lan","sequence":"first","affiliation":[{"name":"Centre For Lipid Research &amp; Chongqing Key Laboratory of Metabolism on Lipid and Glucose Institute For Viral Hepatitis Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) the Second Affiliated Hospital Chongqing Medical 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