Cell line derived from human paraganglioma stained with the BODIPY-carnitine probe.Scientists at the CSIC, FICYT and the FINBA, have developed a fluorescent probe that can enter the mithocondrial matrix of living cells. Mitochondria are organelles in all eukaryotic cells that produce energy for the cell, either from lipids or glucose.
“Something characteristic of mitochondria is that it is extremely difficult to introduce anything into their internal matrix”, explains José Luis Chiara, a CSIC scientist and one of the creators of the probe. “As some bacteria, mitochondria have a double membrane, and the inner one repels virtually everything”.
The new fluorescent probe comprises a highly emissive and photostable fluorophore group, which emits the fluorescence and is technically called BODIPY, and the L-carnitine unit for biolocalization. The latter is recognised by a transporter molecule, the carnitine/acylcarnitine translocase, which moves across the membrane carrying fats from outside, in order to oxidize them and to obtain energy. This enables the probe to enter mitochondria. But, also, enables the probe monitoring this specific transporter. The deficiency or dysfunction of this transporter causes a metabolic síndrome, for which this probe could provide a diagnostic test.
The probe could be also used in cancer therapies. Cancer cells have a boosted metabolism, resulting in uncontrolled cell growth. The fat metabolism is specially boosted. In this sense, the control of lipid transport through the mitochondrial membrane is studied as a an option for the prevention and treatment of some cancers.
Also, this probe could be applied in different fields, for the diagnosis of pathologies and genetic diseases, or to introduce active molecules in the mitochondria.
The probe could be applied for the diagnosis of pathologies and genetic diseases, or to introduce active molecules in the mitochondria
As the scientists explain, “other molecules can be assembled to the BODIPY, the chromophore, for detecting substances or for introducing some drug. If the probe is used just for carrying a drug, not for bioimaging uses, the BODIPY can be replaced for the therapeutic molecule and the L-carnitine unit is then used as a carrier”.
Now, industrial partners are being sought to collaborate through a patent licence agreement.
As an advantage, the scientists highlight that the probe is efficient and selective independently of the cromophore, as well as the cell line tested. Also, the minimalist molecular design simplifies the synthesis process, which is done in one step, and can provide other similar probes with tunable absorption and emission frequencies throughout the visible spectrum depending on the selected BODIPY fluorophore.
Besides the carnitine transporter, the probe can enter the mitochondria by an electrophoretic mechanism, because the probe has a positive charge and the inner of mitochondria has a negative potential. Now, the team is assessing each one of these transport methods for the development of a diagnostic tool, says Chiara.
Contact:
Laura Redondo Gallego
Vicepresidencia Adjunta
de Transferencia
del Conocimiento- CSIC
Tel.: (+34) 915681825