title: Recombinant Buckwheat Trypsin Inhibitor Induces Mitophagy by Directly Targeting Mitochondria and Causes Mitochondrial Dysfunction in Hep G2 Cells.
abstract: Mitochondria are essential targets for cancer chemotherapy and other disease treatments. Recombinant buckwheat trypsin inhibitor (rBTI), a member of the potato type I proteinase inhibitor family, was derived from tartary buckwheat extracts. Our results showed that rBTI directly targeted mitochondria and induced mitochondrial fragmentation and mitophagy. This occurs through enhanced depolarization of the mitochondrial membrane potential, increasing reactive oxygen species (ROS) generation associated with the rise of the superoxide dismutase and catalase activity and glutathione peroxidase (GSH) content, and changes in the GSH/oxidized glutathione ratio. Mild and transient ROS induced by rBTI were shown to be important signaling molecules required to induce Hep G2 mitophagy to remove dysfunctional mitochondria. Furthermore, rBTI could directly induce mitochondrial fragmentation. It was also noted that rBTI highly increased colocalization of mitochondria in treated cells compared to nontreated cells. Tom 20, a subunit of the translocase of the mitochondrial outer membrane complex responsible for recognizing mitochondrial presequences, may be the direct target of rBTI.
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University , Taiyuan 030006, P. R. China.
authors: Zhuanhua
authors: Z
authors: Wang
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University , Taiyuan 030006, P. R. China.
authors: Shanshan
authors: S
authors: Li
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University , Taiyuan 030006, P. R. China.
authors: Rong
authors: R
authors: Ren
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University , Taiyuan 030006, P. R. China.
authors: Jiao
authors: J
authors: Li
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University , Taiyuan 030006, P. R. China.
authors: Xiaodong
authors: X
authors: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019612:Fagopyrum / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D063306:Mitophagy / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014361:Trypsin Inhibitors; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: ROS; mitochondrial fragmentation; mitochondrial membrane potential; mitophagy; rBTI