Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant

Prita R. Asih, Anne Poljak, Michael Kassiou, Yazi D. Ke, Lars M. Ittner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
42 Downloads (Pure)

Abstract

The translocator protein (TSPO) has been implicated in mitochondrial transmembrane cholesterol transport, brain inflammation, and other mitochondrial functions. It is upregulated in glial cells during neuroinflammation in Alzheimer’s disease. High affinity TSPO imaging radioligands are utilized to visualize neuroinflammation. However, this is hampered by the common A147T polymorphism which compromises ligand binding. Furthermore, this polymorphism has been linked to increased risk of neuropsychiatric disorders, and possibly reduces TSPO protein stability. Here, we used immunoprecipitation coupled to mass-spectrometry (IP-MS) to establish a mitochondrial protein binding profile of wild-type (WT) TSPO and the A147T polymorphism variant. Using mitochondria from human glial cells expressing either WT or A147T TSPO, we identified 30 WT TSPO binding partners, yet only 23 for A147T TSPO. Confirming that A147T polymorphism of the TSPO might confer loss of function, we found that one of the identified interactors of WT TSPO, 14-3-3 theta (YWHAQ), a protein involved in regulating mitochondrial membrane proteins, interacts much less with A147T TSPO. Our data presents a network of mitochondrial interactions of TSPO and its A147T polymorphism variant in human glial cells and indicate functional relevance of A147T in mitochondrial protein networks.

Original languageEnglish
Article numbere0254296
Pages (from-to)1-16
Number of pages16
JournalPLoS ONE
Volume17
Issue number5
DOIs
Publication statusPublished - 6 May 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Fingerprint

Dive into the research topics of 'Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant'. Together they form a unique fingerprint.

Cite this