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

A. Kafkova, L. Tilokani, F. Trčka, V. Šrámková, M. Vancová, T. Bílý, J. Nebesářová, J. Prudent, J. Trnka

. 2023 ; 68 (-) : 60-71. [pub] 20221117

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc23004761

Grantová podpora
MC_ UU_00015/7 Medical Research Council - United Kingdom

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.

Citace poskytuje Crossref.org

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$a Triphenylphosphonium (TPP) derivatives are commonly used to target chemical into mitochondria. We show that alkyl-TPP cause reversible, dose- and hydrophobicity-dependent alterations of mitochondrial morphology and function and a selective decrease of mitochondrial inner membrane proteins including subunits of the respiratory chain complexes, as well as components of the mitochondrial calcium uniporter complex. The treatment with alkyl-TPP resulted in the cleavage of the pro-fusion and cristae organisation regulator Optic atrophy-1. The structural and functional effects of alkyl-TPP were found to be reversible and not merely due to loss of membrane potential. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ.
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$a Trčka, Filip $u Laboratory for Metabolism and Bioenergetics, Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Czech Republic
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$a Šrámková, Veronika $u Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Vancová, Marie $u Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Republic; Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic
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$a Prudent, Julien $u Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK
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