2. Academic Validation
  3. Single-organelle visualization tracking natural glycosaminoglycans within mitochondria-lysosome crosstalk for inflammatory homeostasis

Single-organelle visualization tracking natural glycosaminoglycans within mitochondria-lysosome crosstalk for inflammatory homeostasis

  • Int J Biol Macromol. 2025 Jan 27:303:140362. doi: 10.1016/j.ijbiomac.2025.140362.
Ting Sun 1,  Huarong Shao 2,  Ran Wang 3,  Qingkai Zeng 3,  Xintian Shao 4,  Fei Liu 5,  Gang Li 6,  Peixue Ling 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; School of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery System, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China.
  • 2 Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Shandong Academy of Pharmaceutical Science, Jinan, Shandong 250101, China.
  • 3 National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, Shandong 266237, China.
  • 4 School of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery System, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China. Electronic address: shaoxintian@sdfmu.edu.cn.
  • 5 Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Shandong Academy of Pharmaceutical Science, Jinan, Shandong 250101, China. Electronic address: liufei@sdaps.cn.
  • 6 Orthopaedic, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, China. Electronic address: 60170033@sdutcm.edu.cn.
  • 7 School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; National Glycoengineering Research Center, Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, Shandong 266237, China. Electronic address: lingpeixue@sdu.edu.cn.
PMID: 39880268 DOI: 10.1016/j.ijbiomac.2025.140362
Abstract

Glycosaminoglycans (GAGs), as Natural Products with diverse biological activities, play a significant role in regulating inflammatory homeostasis. Nevertheless, the mechanism underlying their intracellular anti-inflammatory properties remains unclear. Herein, we propose a single-organelle visualization tracking framework, leveraging an advanced fluorescent imaging technology combined with labeling methods to dynamically trace the subcellular regulatory mechanisms of GAGs in eliminating inflammatory markers, such as Reactive Oxygen Species (ROS). By utilizing conventional fluorescein isothiocyanate (FITC)-labeled GAGs, we successfully achieved in situ single-organelle visualization of the subcellular localization and intracellular activities of GAGs. Our findings revealed that GAGs enter lysosomes and increase their number and activity, with chondroitin sulfate (CS) exhibiting particularly prominent effects. Significantly, we visually depict that CS-loaded lysosomes selectively cleave ROS-enriched terminal mitochondria, driving mitochondrial fission and reprogramming. These results corroborate that CS regulate mitochondria-lysosome crosstalk to control mitochondrial quality, thereby maintaining intracellular inflammatory homeostasis. Collectively, our work presents an evidence on the single-organelle visualization and regulatory mechanism of GAGs, thereby offering novel perspectives and avenues for researching other Natural Products.

Keywords

Inflammatory homeostasis; Mitochondria-lysosome crosstalk; Mitochondrial reprogramming; Natural glycosaminoglycans; Single-organelle visualization.

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