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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



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.

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


DOI: 10.1002/cbic.201600188


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Funder referenceFunder name
G906919Wellcome Trust Centre for Mitochondrial Research
U105178803Medical Research Council
U105663142Medical Research Council
Medical Research Council (programme no. U105663142)
Work in the laboratory of M.J.G. was supported by the Medical Research Council (programme no.U105178803)
The Wellcome Trust Centre for Mitochondrial Research (G906919)