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.

Department of Pathophysiology 3rd Faculty of Medicine Charles University Prague Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Ceske Budejovice Czech Republic; Faculty of Science University of South Bohemia Ceske Budejovice Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Ceske Budejovice Czech Republic; Laboratory of Electron Microscopy Faculty of Science Charles University Prague Czech Republic

Laboratory for Metabolism and Bioenergetics Department of Biochemistry Cell and Molecular Biology 3rd Faculty of Medicine Charles University Czech Republic

Medical Research Council Mitochondrial Biology Unit University of Cambridge Cambridge Biomedical Campus Cambridge CB2 0XY UK

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