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Title: Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics
Authors: Kam, Antony
Dutta, Bamaprasad
Loo, Shining
Tam, James P.
Sze, Siu Kwan
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2019
Source: Kam, A., Loo, S., Dutta, B., Sze, S. K., & Tam, J. P. (2019). Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics. Journal of Biological Chemistry, 294(11), 4000-4011. doi:10.1074/jbc.RA118.006693
Series/Report no.: Journal of Biological Chemistry
Abstract: Mitochondria are attractive therapeutic targets for developing agents to delay age-related frailty and diseases. However, few promising leads have been identified from natural products. Previously, we identified roseltide rT1, a hyperstable 27-residue cysteine-rich peptide from Hibiscus sabdariffa, as a knottintype neutrophil elastase inhibitor. Here, we show that roseltide rT1 is also a cell-penetrating, mitochondria-targeting peptide that increases ATP production. Results from flow cytometry, live-cell imaging, pulldown assays, and genetically-modified cell lines supported that roseltide rT1 enters cells via glycosaminoglycan- dependent endocytosis, and enters the mitochondria through TOM20, a mitochondrial protein import receptor. We further showed that roseltide rT1 increases cellular ATP production via mitochondrial membrane hyperpolarization. Using biotinylated roseltide rT1 for target identification and proteomic analysis, we showed that human mitochondrial membrane ATP synthase subunit O is an intramitochondrial target. Collectively, these data support our discovery that roseltide rT1 is a first-in-class mitochondria-targeting, cysteine-rich peptide with potentials to be developed into tools to further our understanding of mitochrondria-related diseases.
ISSN: 0021-9258
DOI: 10.1074/jbc.RA118.006693
Rights: © 2019 Kam et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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