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Int. J. Mol. Sci. 2017, 18(4), 879; doi:10.3390/ijms18040879

ρ0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids

1
Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany
2
Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Nobuhiro Nakamura
Received: 6 March 2017 / Revised: 10 April 2017 / Accepted: 11 April 2017 / Published: 20 April 2017
(This article belongs to the Special Issue Ubiquitin System)
View Full-Text   |   Download PDF [2093 KB, uploaded 20 April 2017]   |  

Abstract

Solute carrier (SLC) transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs), such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ0 cells (lacking mitochondrial DNA, mtDNA) compared to parental cells. Here, we elucidated the altered functionality of SLC transporters and their dynamic ubiquitination status by measuring the uptake of several isotopically labeled amino acids in both human osteosarcoma 143B.TK- and ρ0 cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid transporters in ρ0 cells were accompanied by an increased transport rate, which leads to higher levels of amino acids in the cell. Finding SLC transport enhancers is an aim of the pharmaceutical industry in order to compensate for loss of function mutations in these genes. Thus, the ubiquitination status of SLC transporters could be an indicator for their functionality, but evidence for a direct connection between de-ubiquitination and transporter activity has to be further elucidated. View Full-Text
Keywords: SLC transporter; ubiquitination; amino acids; pulse chase; ρ0 cells SLC transporter; ubiquitination; amino acids; pulse chase; ρ0 cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Medina, A.B.; Banaszczak, M.; Ni, Y.; Aretz, I.; Meierhofer, D. ρ0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids. Int. J. Mol. Sci. 2017, 18, 879.

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