3 March 2021

Together with colleagues from the MRC-Mitochondrial Biology Unit (University of Cambridge), Tom Schirris, theme Metabolic disorders, published a research article entitled “Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition” in Theranostics.

An increasing number of commonly prescribed drugs are known to interfere with mitochondrial function, causing cellular toxicity, but the underlying mechanisms are largely unknown. Although often not considered, mitochondrial transport proteins form a significant class of potential mitochondrial off-targets. So far, most drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC), which exchanges cytosolic ADP for mitochondrial ATP. However, these claims have never been validated and a simple, direct model system to evaluate and compare drug-induced AAC inhibition is lacking. Here, we provide a characterization of the human AAC1 and demonstrate its relevance to study drug-induced inhibition. Our work also paves the way to study many other mitochondrial transport proteins that could be relevant drug off-targets. Consequently, these analyses will eventually provide insights in the role of mitochondrial transport proteins in drug-induced mitochondrial dysfunction and will thereby contribute to the development of drugs with an enhanced safety profile.

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