@article{59d4d2497ae540498747d402defa1cf5,
title = "Antimicrobial peptide TP4 targets mitochondrial adenine nucleotide translocator 2",
abstract = "Tilapiapiscidin(TP)4isanantimicrobialpeptidederivedfromNiletilapia(Oreochromisniloticus), 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.",
keywords = "Adenine nucleotide translocator 2 (ANT2), Antimicrobial peptide (AMP), Tilapia piscidin 4 (TP4)",
author = "Su, {Bor Chyuan} and Liu, {Yi Chung} and Ting, {Chen Hung} and Lyu, {Ping Chiang} and Chen, {Jyh Yih}",
note = "Funding Information: Acknowledgments: We thank Marcus J. Calkins for language editing. We appreciate the Structural proteomics and pharmaceutical application service provided by the BP Bioinformatics Core (http://www.tbi.org.tw), funded by National Core Facility for Biopharmaceuticals (NCFB), MOST 108-2319-B-400-001, for the molecular docking experiments. We thank the GLP Laboratory, protein science and service division. We thank Mithra Biotechnology Inc. for the protein identification studies. This work was supported by a PI quota to Jyh-Yih Chen from the Marine Research Station, ICOB. Funding Information: Funding: This work was financially supported by the iEGG and Animal Biotechnology Center from the Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-109-S-0023-A) in Taiwan. This work was partly financially supported by the 109-2313-B-001-007-MY3, 109-2622-B-001-002-CC1, or 108-2313-B-001-006—from the Ministry of Science and Technology (Taiwan). The funders played no part in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: This work was financially supported by the iEGG and Animal Biotechnology Center from the Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-109-S-0023-A) in Taiwan. This work was partly financially supported by the 109-2313-B-001-007-MY3, 109-2622-B-001-002-CC1, or 108-2313-B-001-006?from the Ministry of Science and Technology (Taiwan). The funders played no part in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
doi = "10.3390/MD18080417",
language = "English",
volume = "18",
journal = "Marine Drugs",
issn = "1660-3397",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",
}
