Recombinant Buckwheat Trypsin Inhibitor Induces Mitophagy by Directly Targeting Mitochondria and Causes Mitochondrial Dysfunction in Hep G2 Cells

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...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2015-09, Vol.63 (35), p.7795-7804
Main Authors: Wang, Zhuanhua, Li, Shanshan, Ren, Rong, Li, Jiao, Cui, Xiaodong
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Fagopyrum - chemistry
Glutathione Peroxidase - genetics
Glutathione Peroxidase - metabolism
Hep G2 Cells
Humans
Liver Neoplasms - enzymology
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - physiopathology
Mitochondria - drug effects
Mitochondria - enzymology
Mitochondria - physiology
Mitochondrial Degradation - drug effects
Plant Extracts - pharmacology
Reactive Oxygen Species - metabolism
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
Trypsin Inhibitors - pharmacology
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Summary: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.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.5b02644