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Open AccessArticle

Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

1
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
2
Institute of Population Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli County 350, Taiwan
3
Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan
4
Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 300, Taiwan
5
The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2020, 18(8), 417; https://doi.org/10.3390/md18080417
Received: 21 July 2020 / Revised: 4 August 2020 / Accepted: 7 August 2020 / Published: 9 August 2020
(This article belongs to the Special Issue Advances in Marine Antimicrobial Peptides)
Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism. View Full-Text
Keywords: antimicrobial peptide (AMP); tilapia piscidin 4 (TP4); adenine nucleotide translocator 2 (ANT2) antimicrobial peptide (AMP); tilapia piscidin 4 (TP4); adenine nucleotide translocator 2 (ANT2)
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Su, B.-C.; Liu, Y.-C.; Ting, C.-H.; Lyu, P.-C.; Chen, J.-Y. Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2. Mar. Drugs 2020, 18, 417.

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