Cholesterol- dependent enzyme activity of human TSPO1

• 成果类型: Article
• 署名作者: Qiu, Weihua; Trinh, Thi Kim Hoang; Catalano, Claudio; Mehta, Akul; Desai, Umesh R.; Kellogg, Glen E.; Hendrickson, Wayne A.; Guo, Youzhong
• 署名单位: Virginia Commonwealth University; Virginia Commonwealth University; Columbia University; Columbia University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11750
• DOI: 10.1073/pnas.2323045122
• 发表日期: 2025-04-01
• 关键词: translocator protein tspo; 18 kda; benzodiazepine-receptor; crystal-structures; ligand-binding; target; mutant; state

摘要

The amino acid sequence of the tryptophan- rich sensory proteins (TSPO) is substantially conserved throughout all kingdoms of life. Human mitochondrial TSPO1 (HsTSPO1) binds to porphyrins and steroids, although its interactions with these molecules remains unknown. HsTSPO1 is associated with numerous physiological and pathological disorders, but the underlying molecular mechanisms are unknown. Here, we disclose the finding of human mitochondrial TSPO as a cholesterol- dependent protoporphyrin IX oxygenase. The results of our biochemical characterization are consistent with structural data and evolutionary analysis. The dependence of HsTSPO1 activity on cholesterol may be the result of the coevolution of this membrane protein with the membrane system. Our study provides a molecular foundation for comprehending the various roles played by mitochondrial TSPO in normal physiological and pathological situations.