Antimicrobial peptide TP4 targets mitochondrial adenine nucleotide translocator 2

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number417
JournalMarine Drugs
Volume18
Issue number8
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Adenine nucleotide translocator 2 (ANT2)
  • Antimicrobial peptide (AMP)
  • Tilapia piscidin 4 (TP4)

ASJC Scopus subject areas

  • Drug Discovery

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