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

Jonathan Hosler1, Ngoc Hoang1, Kristin Shirey Edwards1

  • 1Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, United States.

Mitochondrion
|May 18, 2023
PubMed

Insights

Micafungin, an antifungal drug, causes fungal mitochondria to swell and rupture by altering the inner membrane anion channel (IMAC). This drug interaction leads to the release of cytochrome c, highlighting a novel mechanism for antifungal activity.

Area of Science:

  • Biochemistry
  • Mycology
  • Pharmacology

Background:

  • Micafungin is a cyclic lipopeptide antifungal agent.
  • Its mechanism of action may involve fungal mitochondria.
  • Human mitochondria are protected from micafungin due to membrane impermeability.

Purpose of the Study:

  • To investigate the effect of micafungin on isolated fungal mitochondria.
  • To elucidate the role of the inner membrane anion channel (IMAC) in micafungin's antifungal activity.

Main Methods:

  • Experiments were conducted using isolated mitochondria.
  • Mitochondrial swelling and rupture were observed.
  • Cytochrome c release was measured.
  • The function of the inner membrane anion channel (IMAC) was analyzed.

Main Results:

  • Micafungin induced rapid salt uptake, leading to mitochondrial swelling and rupture.
  • The release of cytochrome c was observed following mitochondrial rupture.
  • Micafungin altered the inner membrane anion channel (IMAC), enabling the transfer of both cations and anions.
  • A model was proposed where anionic micafungin binding to IMAC facilitates ion pair transfer.

Conclusions:

  • Micafungin's antifungal activity is mediated, in part, by targeting fungal mitochondria.
  • The drug disrupts mitochondrial integrity by altering IMAC function.
  • This disruption leads to the release of cytochrome c, a key apoptotic factor.
Keywords:
Cyclic lipopeptideInner membrane anion channelIon channelMicafunginMitochondrial ion channelMitochondrial respiratory chain complexcytochrome c release

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