Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.

Mitochondrial defects can cause a variety of human diseases and protective mechanisms exist to maintain mitochondrial functionality. Imbalances in mitochondrial proteostasis trigger a transcriptional program, termed mitochondrial unfolded protein response (mtUPR). However, the temporal sequence of e...

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Autores principales:	Daniel Poveda-Huertes, Asli Aras Taskin, Ines Dhaouadi, Lisa Myketin, Adinarayana Marada, Lukas Habernig, Sabrina Büttner, F-Nora Vögtle
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/4bc527a29d51462a9590e7b42257a8e8
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spelling	oai:doaj.org-article:4bc527a29d51462a9590e7b42257a8e82021-12-02T20:02:57ZIncreased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.1553-73901553-740410.1371/journal.pgen.1009664https://doaj.org/article/4bc527a29d51462a9590e7b42257a8e82021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009664https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Mitochondrial defects can cause a variety of human diseases and protective mechanisms exist to maintain mitochondrial functionality. Imbalances in mitochondrial proteostasis trigger a transcriptional program, termed mitochondrial unfolded protein response (mtUPR). However, the temporal sequence of events in mtUPR is unclear and the consequences on mitochondrial protein import are controversial. Here, we have quantitatively analyzed all main import pathways into mitochondria after different time spans of mtUPR induction. Kinetic analyses reveal that protein import into all mitochondrial subcompartments strongly increases early upon mtUPR and that this is accompanied by rapid remodelling of the mitochondrial signature lipid cardiolipin. Genetic inactivation of cardiolipin synthesis precluded stimulation of protein import and compromised cellular fitness. At late stages of mtUPR upon sustained stress, mitochondrial protein import efficiency declined. Our work clarifies the enigma of protein import upon mtUPR and identifies sequential mtUPR stages, in which an early increase in protein biogenesis to restore mitochondrial proteostasis is followed by late stages characterized by a decrease in import capacity upon prolonged stress induction.Daniel Poveda-HuertesAsli Aras TaskinInes DhaouadiLisa MyketinAdinarayana MaradaLukas HabernigSabrina BüttnerF-Nora VögtlePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009664 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Daniel Poveda-Huertes Asli Aras Taskin Ines Dhaouadi Lisa Myketin Adinarayana Marada Lukas Habernig Sabrina Büttner F-Nora Vögtle Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
description	Mitochondrial defects can cause a variety of human diseases and protective mechanisms exist to maintain mitochondrial functionality. Imbalances in mitochondrial proteostasis trigger a transcriptional program, termed mitochondrial unfolded protein response (mtUPR). However, the temporal sequence of events in mtUPR is unclear and the consequences on mitochondrial protein import are controversial. Here, we have quantitatively analyzed all main import pathways into mitochondria after different time spans of mtUPR induction. Kinetic analyses reveal that protein import into all mitochondrial subcompartments strongly increases early upon mtUPR and that this is accompanied by rapid remodelling of the mitochondrial signature lipid cardiolipin. Genetic inactivation of cardiolipin synthesis precluded stimulation of protein import and compromised cellular fitness. At late stages of mtUPR upon sustained stress, mitochondrial protein import efficiency declined. Our work clarifies the enigma of protein import upon mtUPR and identifies sequential mtUPR stages, in which an early increase in protein biogenesis to restore mitochondrial proteostasis is followed by late stages characterized by a decrease in import capacity upon prolonged stress induction.
format	article
author	Daniel Poveda-Huertes Asli Aras Taskin Ines Dhaouadi Lisa Myketin Adinarayana Marada Lukas Habernig Sabrina Büttner F-Nora Vögtle
author_facet	Daniel Poveda-Huertes Asli Aras Taskin Ines Dhaouadi Lisa Myketin Adinarayana Marada Lukas Habernig Sabrina Büttner F-Nora Vögtle
author_sort	Daniel Poveda-Huertes
title	Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
title_short	Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
title_full	Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
title_fullStr	Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
title_full_unstemmed	Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.
title_sort	increased mitochondrial protein import and cardiolipin remodelling upon early mtupr.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4bc527a29d51462a9590e7b42257a8e8
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Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.

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