Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR. / Poveda-Huertes, Daniel; Taskin, Asli Aras; Dhaouadi, Ines; Myketin, Lisa; Marada, Adinarayana; Habernig, Lukas; Büttner, Sabrina; Vögtle, F-Nora.
In: PLOS Genetics, Vol. 17, No. 7, e1009664, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR
AU - Poveda-Huertes, Daniel
AU - Taskin, Asli Aras
AU - Dhaouadi, Ines
AU - Myketin, Lisa
AU - Marada, Adinarayana
AU - Habernig, Lukas
AU - Büttner, Sabrina
AU - Vögtle, F-Nora
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Cardiolipins/metabolism
KW - Mitochondria/genetics
KW - Mitochondrial Proteins/metabolism
KW - Protein Biosynthesis
KW - Protein Transport/genetics
KW - Saccharomyces cerevisiae/genetics
KW - Saccharomyces cerevisiae Proteins/genetics
KW - Unfolded Protein Response/genetics
U2 - 10.1371/journal.pgen.1009664
DO - 10.1371/journal.pgen.1009664
M3 - Journal article
C2 - 34214073
VL - 17
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 7
M1 - e1009664
ER -
ID: 391634384