Biomaterial Database

The cyclic lipopeptide micafungin induces rupture of isolated mitochondria by reprograming the mitochondrial inner membrane anion channel. 2023

Jonathan Hosler, and Ngoc Hoang, and Kristin Shirey Edwards

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

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.

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077551	Micafungin	A cyclic lipo-hexapeptide echinocandin antifungal agent that is used for the treatment and prevention of CANDIDIASIS.	FK 463,FK-463,FK463,Micafungin Sodium,Mycamine
D000838	Anions	Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.	Anion
D051336	Mitochondrial Membranes	The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).	Inner Mitochondrial Membrane,Mitochondrial Membrane, Inner,Mitochondrial Membrane, Outer,Outer Mitochondrial Membrane,Inner Mitochondrial Membranes,Membrane, Inner Mitochondrial,Membrane, Mitochondrial,Membrane, Outer Mitochondrial,Membranes, Inner Mitochondrial,Membranes, Mitochondrial,Membranes, Outer Mitochondrial,Mitochondrial Membrane,Mitochondrial Membranes, Inner,Mitochondrial Membranes, Outer,Outer Mitochondrial Membranes