Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics
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 sabdarif...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/89096 http://hdl.handle.net/10220/48850 |
| _version_ | 1811687884724371456 |
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| author | Kam, Antony Dutta, Bamaprasad Loo, Shining Tam, James P. Sze, Siu Kwan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Kam, Antony Dutta, Bamaprasad Loo, Shining Tam, James P. Sze, Siu Kwan |
| author_sort | Kam, Antony |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:23:24Z |
| format | Journal Article |
| id | ntu-10356/89096 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:23:24Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/890962023-02-28T17:02:23Z Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics Kam, Antony Dutta, Bamaprasad Loo, Shining Tam, James P. Sze, Siu Kwan School of Biological Sciences DRNTU::Science::Biological sciences Bioenergetics Peptides 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. Accepted version 2019-06-20T01:54:22Z 2019-12-06T17:17:46Z 2019-06-20T01:54:22Z 2019-12-06T17:17:46Z 2019 Journal Article 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 0021-9258 https://hdl.handle.net/10356/89096 http://hdl.handle.net/10220/48850 10.1074/jbc.RA118.006693 en Journal of Biological Chemistry © 2019 Kam et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. 15 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Bioenergetics Peptides Kam, Antony Dutta, Bamaprasad Loo, Shining Tam, James P. Sze, Siu Kwan Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title | Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title_full | Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title_fullStr | Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title_full_unstemmed | Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title_short | Plant-derived mitochondria-targeting cysteine-rich peptide modulates cellular bioenergetics |
| title_sort | plant derived mitochondria targeting cysteine rich peptide modulates cellular bioenergetics |
| topic | DRNTU::Science::Biological sciences Bioenergetics Peptides |
| url | https://hdl.handle.net/10356/89096 http://hdl.handle.net/10220/48850 |
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