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

Medina, A. B., Banaszczak, M., Ni, Y., Aretz, I., & Meierhofer, D. (2017). ρ⁰ Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids. International Journal of Molecular Sciences, 18: E879. doi:10.3390/ijms18040879.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D329-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-D41B-5
Genre: Journal Article

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 Creators:
Medina, André Bordinassi, Author
Banaszczak, Marcin , Author
Ni, Yang1, Author              
Aretz, Ina1, Author              
Meierhofer, David1, Author              
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: SLC transporter; amino acids; pulse chase; ubiquitination; ρ0 cells
 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.

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Language(s): eng - English
 Dates: 2017-04-20
 Publication Status: Published online
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.3390/ijms18040879
 Degree: -

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Title: International Journal of Molecular Sciences
  Abbreviation : Int. J. Mol. Sci.
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI AG
Pages: 4 Volume / Issue: 18 Sequence Number: E879 Start / End Page: - Identifier: ISSN: 1422-0067
CoNE: /journals/resource/1422-0067