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Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry

Lookup NU author(s): Dr Kurt Hoogewijs, Professor Robert Lightowlers

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

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.

Publication metadata

Author(s): Hoogewijs K, James AM, Smith RAJ, Gait MJ, Murphy MP, Lightowlers RN

Publication type: Article

Publication status: Published

Journal: ChemBioChem

Year: 2016

Volume: 17

Issue: 14

Pages: 1312-1316

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

URL: http://dx.doi.org/10.1002/cbic.201600188

DOI: 10.1002/cbic.201600188

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