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bioRxiv · 10.1101/2021.03.09.434520

Selective and reversible disruption of mitochondrial inner membrane protein complexes by lipophilic cations

Kafkova, A.·Tilokani, L.·Trcka, F.·Sramkova, V.·Vancova, M.·Bily, T.·Nebesarova, J.·Prudent, J.·Trnka, J.
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Abstract

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.

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Kafkova, A., Tilokani, L., Trcka, F., Sramkova, V., Vancova, M., Bily, T., Nebesarova, J., Prudent, J., Trnka, J.. 2021-03-09. Selective and reversible disruption of mitochondrial inner membrane protein complexes by lipophilic cations. https://doi.org/10.1101/2021.03.09.434520

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