1. Shedding light on the mitochondrial matrix through a functional membrane transporter
- Author
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Inmaculada García-Moreno, María D. Chiara, Jose Luis Chiara, Alberto Blázquez-Moraleja, Virginia Martínez-Martínez, Delia Álvarez-Fernández, Iñigo López Arbeloa, Ruth Prieto-Montero, Ines Sáenz-de-Santa María, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Eusko Jaurlaritza, Instituto de Salud Carlos III, Blázquez, Alberto, Sáenz-deChiara-Santa María, Inés, Chiara, María D., García-Moreno, Inmaculada, Prieto-Montero, Ruth, Martínez-Martínez, Virginia, López Arbeloa, Iñigo, Chiara, José Luis, Blázquez, Alberto [0000-0003-1375-930X], Sáenz-deChiara-Santa María, Inés [0000-0002-1868-3001], Chiara, María D. [0000-0002-1112-1583], García-Moreno, Inmaculada [0000-0002-8682-3715], Prieto-Montero, Ruth [0000-0001-6372-563X], Martínez-Martínez, Virginia [0000-0001-7551-3714], López Arbeloa, Iñigo [0000-0002-8440-6600], and Chiara, José Luis [0000-0002-8153-1852]
- Subjects
BODIPY dyes ,biology ,Chemistry ,MItochondria ,Transporter ,General Chemistry ,Carnitine shuttle ,Mitochondrion ,Fluorescent dyes ,Transport protein ,chemistry.chemical_compound ,Cell microscopy ,Biomimetics ,biology.protein ,medicine ,Biophysics ,Translocase ,Carnitine ,BODIPY ,Inner mitochondrial membrane ,medicine.drug - Abstract
Electronic Supplementary Information (ESI) available: Supplementary figures and tables and copies of the 1H and 13C NMR (1D and 2D) spectra of the new compounds., 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 FBODIPYs 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., We gratefully acknowledge the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI), and European Regional Development Fund (ERDF) (projects MAT2017-83856-C3-1-P, MAT2017-83856-C3-3-P, and MAT2015-68837-REDT), Gobierno Vasco (IT912-16), and the Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (CIBERONC and PI17/01901) for financial support. A. B.-M. and R. P. M. thank MCIU, AEI and ERDF, and UPV-EHU for a FPI predoctoral contract and predoctoral fellowship, respectively
- Published
- 2021