环状脂肽米卡芬净通过重编程线粒体内膜阴离子通道诱导分离的线粒体破裂。
The cyclic lipopeptide micafungin induces rupture of isolated mitochondria by reprograming the mitochondrial inner membrane anion channel.
机构信息
Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, United States.
Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, United States.
出版信息
Mitochondrion. 2023 Jul;71:50-62. doi: 10.1016/j.mito.2023.05.004. Epub 2023 May 16.
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.
药物米卡芬净是一种环状脂肽，能与膜蛋白相互作用，具有抗真菌活性，其作用机制可能与抑制真菌的线粒体功能有关。在人体内，由于米卡芬净无法穿过细胞质膜，因此线粒体不会受到影响。本研究利用分离的线粒体发现，米卡芬净可诱导盐的摄取，导致线粒体迅速肿胀和破裂，并释放细胞色素 c。米卡芬净可改变内膜阴离子通道（IMAC），从而同时转运阳离子和阴离子。我们推测，带负电荷的米卡芬净与 IMAC 结合后，会吸引阳离子进入离子通道，从而快速转运离子对。
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