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ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway

Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting...

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Autores principales: Xiao, Tianyao, Shakya, Viplendra PS, Hughes, Adam L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898604/
https://www.ncbi.nlm.nih.gov/pubmed/33479049
http://dx.doi.org/10.26508/lsa.202000918
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author Xiao, Tianyao
Shakya, Viplendra PS
Hughes, Adam L
author_facet Xiao, Tianyao
Shakya, Viplendra PS
Hughes, Adam L
author_sort Xiao, Tianyao
collection PubMed
description Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting to other organelles. Amongst organelles, the ER has emerged as a key destination for a subset of non-imported mitochondrial proteins. However, how ER targeting of various types of mitochondrial proteins is achieved remains incompletely understood. Here, we show that the ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway. Overall, this study outlines an important role for the GET complex in ER targeting of non-imported mitochondrial carrier proteins.
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spelling pubmed-78986042021-03-23 ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway Xiao, Tianyao Shakya, Viplendra PS Hughes, Adam L Life Sci Alliance Research Articles Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting to other organelles. Amongst organelles, the ER has emerged as a key destination for a subset of non-imported mitochondrial proteins. However, how ER targeting of various types of mitochondrial proteins is achieved remains incompletely understood. Here, we show that the ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway. Overall, this study outlines an important role for the GET complex in ER targeting of non-imported mitochondrial carrier proteins. Life Science Alliance LLC 2021-01-21 /pmc/articles/PMC7898604/ /pubmed/33479049 http://dx.doi.org/10.26508/lsa.202000918 Text en © 2021 Xiao et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Xiao, Tianyao
Shakya, Viplendra PS
Hughes, Adam L
ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title_full ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title_fullStr ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title_full_unstemmed ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title_short ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
title_sort er targeting of non-imported mitochondrial carrier proteins is dependent on the get pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898604/
https://www.ncbi.nlm.nih.gov/pubmed/33479049
http://dx.doi.org/10.26508/lsa.202000918
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