Laboratory for Metabolism and Bioenergetics, Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Czech Republic.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Mitochondrion. 2023 Jan;68:60-71. doi: 10.1016/j.mito.2022.11.006. Epub 2022 Nov 17.
Triphenylphosphonium (TPP) derivatives are commonly used to target chemical into mitochondria. We show that alkyl-TPP cause reversible, dose- and hydrophobicity-dependent alterations of mitochondrial morphology and function and a selective decrease of mitochondrial inner membrane proteins including subunits of the respiratory chain complexes, as well as components of the mitochondrial calcium uniporter complex. The treatment with alkyl-TPP resulted in the cleavage of the pro-fusion and cristae organisation regulator Optic atrophy-1. The structural and functional effects of alkyl-TPP were found to be reversible and not merely due to loss of membrane potential. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ.
三苯基膦(TPP)衍生物常用于将化学物质靶向线粒体。我们发现,烷基-TPP 可引起线粒体形态和功能的可逆、剂量和疏水性依赖性改变,以及线粒体内膜蛋白的选择性减少,包括呼吸链复合物的亚基以及线粒体钙单向转运体复合物的组成部分。烷基-TPP 的处理导致融合前和嵴组织调节剂视神经萎缩-1 的裂解。烷基-TPP 的结构和功能影响是可逆的,不仅仅是由于膜电位的丧失。类似的效果也在靶向线粒体的抗氧化剂 MitoQ 中观察到。