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Lookup NU author(s): Dr Kurt Hoogewijs,
Professor Robert Lightowlers
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mitochondria are central to health and disease, hence there is considerable interest in developing mitochondria-targeted therapies that require the delivery of peptides or nucleic acid oligomers. However, progress has been impeded by the lack of a measure of mitochondrial import of these molecules. Here, we address this need by quantitatively detecting molecules within the mitochondrial matrix. We used a mitochondria-targeted cyclooctyne (MitoOct) that accumulates several-hundredfold in the matrix, driven by the membrane potential. There, MitoOct reacts through click chemistry with an azide on the target molecule to form a diagnostic product that can be quantified by mass spectrometry. Because the membrane potential-dependent MitoOct concentration in the matrix is essential for conjugation, we can now determine definitively whether a putative mitochondrion-targeted molecule reaches the matrix. This "ClickIn" approach will facilitate development of mitochondria-targeted therapies.
Author(s): Hoogewijs K, James AM, Smith RAJ, Gait MJ, Murphy MP, Lightowlers RN
Publication type: Article
Publication status: Published
Print publication date: 15/07/2016
Online publication date: 25/05/2016
Acceptance date: 28/04/2016
Date deposited: 21/10/2016
ISSN (print): 1439-4227
ISSN (electronic): 1439-7633
Publisher: WILEY-VCH Verlag
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