The cyclic lipopeptide micafungin induces rupture of isolated mitochondria by reprograming the mitochondrial inner membrane anion channel

Mitochondrion. 2023 Jul:71:50-62. doi: 10.1016/j.mito.2023.05.004. Epub 2023 May 16.

Abstract

The antifungal activity of the drug micafungin, a cyclic lipopeptide that interacts with membrane proteins, may involve inhibition of fungal mitochondria. In humans, mitochondria are spared by the inability of micafungin to cross the cytoplasmic membrane. Using isolated mitochondria, we find that micafungin initiates the uptake of salts, causing rapid swelling and rupture of mitochondria with release of cytochrome c. The inner membrane anion channel (IMAC) is altered by micafungin to transfer both cations and anions. We propose that binding of anionic micafungin to IMAC attracts cations into the ion pore for the rapid transfer of ion pairs.

Keywords: Cyclic lipopeptide; Inner membrane anion channel; Ion channel; Micafungin; Mitochondrial ion channel; Mitochondrial respiratory chain complex; cytochrome c release.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anions / metabolism
  • Humans
  • Ion Channels / metabolism
  • Micafungin / metabolism
  • Mitochondria* / metabolism
  • Mitochondrial Membranes* / metabolism

Substances

  • Micafungin
  • Anions
  • Ion Channels