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First‐in‐class Naturally ‐ occurring Bioenergetic Peptide from Hibiscus sabdariffa
Author(s) -
Kam Antony,
Loo Shining,
Tam James P
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb241
Subject(s) - hibiscus sabdariffa , neurodegeneration , mitochondrion , peptide , biochemistry , biology , chemistry , pharmacology , microbiology and biotechnology , traditional medicine , medicine , disease , pathology
Mitochondria produce more than 90% of cellular energy and defects in energy metabolism are a common cause of age‐related diseases1. These diseases include cardiovascular disease, diabetes, neurodegeneration and fatigue2. In a program to identify potential therapeutics against age‐related diseases, we have identified cysteine‐rich peptides, designated as roseltides, from the medicinal plant Hibiscus sabdariffa . Hibiscus sabdariffa of the Malvaceae family, commonly known as roselle, is a shrub cultivated in South‐east Asian countries. The dark red fruit is used to make drinks, syrups and jams. As a folk medicine, it has been used for treating diabetes, cardiovascular and neurodegeneration‐related diseases3. Here, we report the discovery of roseltide rT1, a bioenergetic‐mitochondria‐targeting peptide from Hibiscus sabdariffa that improves bioenergy traits. Roseltide rT1 was isolated and purified through repeated rounds of liquid chromatography. Using a combination of transriptomic and proteomic methods, roseltide rT1 is identified as a 27‐residue peptide with high metabolic stability4. Roseltide rT1 is a cationic and amphipathic peptide which is favorable for cell‐penetration. Using flow cytometry and live‐cell confocal microscopy, we demonstrated that roseltide rT1 is internalized into living cells via endocytosis. Upon cell entry, roseltide rT1 escapes the endosome and localizes to the mitochondria. Functionally, roseltide rT1 increases cellular ATP level. Taken together, this study highlights the discovery of roseltide rT1, as the first naturally‐occurring mitochondria‐targeting peptide with enhancing properties of ATP production. The features of roseltide rT1 display potential as a new mitochondrial‐targeting agent with therapeutic potentials for mitochondrial dysfunctions. Support or Funding Information This project was supported in part by the National Research Foundation (NRF‐CRP8‐2011‐05) of the Prime Minister's Office of Singapore.