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Shedding light on the mitochondrial matrix through a functional membrane transporter

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Abstract

The first fluorescent probes that are actively channeled into the mitochondrial matrix by a specific mitochondrial membrane transporter in living cells have been developed. The new functional probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through the common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. The obtained experimental evidence supports carnitine–acylcarnitine translocase (CACT) as the key transporter protein for BCTs, which behave therefore as acylcarnitine biomimetics. This simple structural design can be readily extended to other structurally diverse starting F-BODIPYs to obtain BCTs with varied emission wavelengths along the visible and NIR spectral regions and with multifunctional capabilities. BCTs are the first fluorescent derivatives of carnitine to be used in cell microscopy and stand as promising research tools to explore the role of the carnitine shuttle system in cancer and metabolic diseases. Extension of this approach to other small-molecule mitochondrial transporters is envisaged.

Graphical abstract: Shedding light on the mitochondrial matrix through a functional membrane transporter

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Article information


Submitted
25 Sep 2019
Accepted
08 Dec 2019
First published
09 Dec 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020, Advance Article
Article type
Edge Article

Shedding light on the mitochondrial matrix through a functional membrane transporter

A. Blázquez-Moraleja, I. Sáenz-de-Santa María, M. D. Chiara, D. Álvarez-Fernández, I. García-Moreno, R. Prieto-Montero, V. Martínez-Martínez, I. López Arbeloa and J. L. Chiara, Chem. Sci., 2020, Advance Article , DOI: 10.1039/C9SC04852A

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