Antimicrobial peptide TP4 targets mitochondrial adenine nucleotide translocator 2

Bor Chyuan Su, Yi Chung Liu, Chen Hung Ting, Ping Chiang Lyu, Jyh Yih Chen

研究成果: 雜誌貢獻文章同行評審

12 引文 斯高帕斯(Scopus)


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.
期刊Marine Drugs
出版狀態已發佈 - 2020

ASJC Scopus subject areas

  • 藥物發現


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