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An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates

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An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates. / Poveda-Huertes, Daniel; Matic, Stanka; Marada, Adinarayana; Habernig, Lukas; Licheva, Mariya; Myketin, Lisa; Gilsbach, Ralf; Tosal-Castano, Sergi; Papinski, Daniel; Mulica, Patrycja; Kretz, Oliver; Kücükköse, Cansu; Taskin, Asli Aras; Hein, Lutz; Kraft, Claudine; Büttner, Sabrina; Meisinger, Chris; Vögtle, F-Nora.

In: MOL CELL, Vol. 77, No. 1, 02.01.2020, p. 180-188.e9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Poveda-Huertes, D, Matic, S, Marada, A, Habernig, L, Licheva, M, Myketin, L, Gilsbach, R, Tosal-Castano, S, Papinski, D, Mulica, P, Kretz, O, Kücükköse, C, Taskin, AA, Hein, L, Kraft, C, Büttner, S, Meisinger, C & Vögtle, F-N 2020, 'An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates', MOL CELL, vol. 77, no. 1, pp. 180-188.e9. https://doi.org/10.1016/j.molcel.2019.09.026

APA

Poveda-Huertes, D., Matic, S., Marada, A., Habernig, L., Licheva, M., Myketin, L., Gilsbach, R., Tosal-Castano, S., Papinski, D., Mulica, P., Kretz, O., Kücükköse, C., Taskin, A. A., Hein, L., Kraft, C., Büttner, S., Meisinger, C., & Vögtle, F-N. (2020). An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates. MOL CELL, 77(1), 180-188.e9. https://doi.org/10.1016/j.molcel.2019.09.026

Vancouver

Poveda-Huertes D, Matic S, Marada A, Habernig L, Licheva M, Myketin L et al. An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates. MOL CELL. 2020 Jan 2;77(1):180-188.e9. https://doi.org/10.1016/j.molcel.2019.09.026

Bibtex

@article{92147ad33bfa496a941fb88c17a945d0,
title = "An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates",
abstract = "The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense.",
keywords = "Cell Death/physiology, Cell Nucleus/metabolism, DNA, Mitochondrial/metabolism, Membrane Potentials/physiology, Mitochondria/metabolism, Protein Biosynthesis/physiology, Repressor Proteins/metabolism, Saccharomyces cerevisiae Proteins/metabolism, Saccharomyces cerevisiae/metabolism, Transcription Factors/metabolism, Transcription, Genetic/physiology, Unfolded Protein Response/physiology",
author = "Daniel Poveda-Huertes and Stanka Matic and Adinarayana Marada and Lukas Habernig and Mariya Licheva and Lisa Myketin and Ralf Gilsbach and Sergi Tosal-Castano and Daniel Papinski and Patrycja Mulica and Oliver Kretz and Cansu K{\"u}c{\"u}kk{\"o}se and Taskin, {Asli Aras} and Lutz Hein and Claudine Kraft and Sabrina B{\"u}ttner and Chris Meisinger and F-Nora V{\"o}gtle",
note = "Copyright {\textcopyright} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = jan,
day = "2",
doi = "10.1016/j.molcel.2019.09.026",
language = "English",
volume = "77",
pages = "180--188.e9",
journal = "MOL CELL",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates

AU - Poveda-Huertes, Daniel

AU - Matic, Stanka

AU - Marada, Adinarayana

AU - Habernig, Lukas

AU - Licheva, Mariya

AU - Myketin, Lisa

AU - Gilsbach, Ralf

AU - Tosal-Castano, Sergi

AU - Papinski, Daniel

AU - Mulica, Patrycja

AU - Kretz, Oliver

AU - Kücükköse, Cansu

AU - Taskin, Asli Aras

AU - Hein, Lutz

AU - Kraft, Claudine

AU - Büttner, Sabrina

AU - Meisinger, Chris

AU - Vögtle, F-Nora

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/1/2

Y1 - 2020/1/2

N2 - The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense.

AB - The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense.

KW - Cell Death/physiology

KW - Cell Nucleus/metabolism

KW - DNA, Mitochondrial/metabolism

KW - Membrane Potentials/physiology

KW - Mitochondria/metabolism

KW - Protein Biosynthesis/physiology

KW - Repressor Proteins/metabolism

KW - Saccharomyces cerevisiae Proteins/metabolism

KW - Saccharomyces cerevisiae/metabolism

KW - Transcription Factors/metabolism

KW - Transcription, Genetic/physiology

KW - Unfolded Protein Response/physiology

U2 - 10.1016/j.molcel.2019.09.026

DO - 10.1016/j.molcel.2019.09.026

M3 - SCORING: Journal article

C2 - 31630969

VL - 77

SP - 180-188.e9

JO - MOL CELL

JF - MOL CELL

SN - 1097-2765

IS - 1

ER -