PT  - JOURNAL ARTICLE
AU  - Carina Groh
AU  - Per Haberkant
AU  - Frank Stein
AU  - Sebastian Filbeck
AU  - Stefan Pfeffer
AU  - Mikhail M Savitski
AU  - Felix Boos
AU  - Johannes M Herrmann
TI  - Mitochondrial dysfunction rapidly modulates the abundance and thermal stability of cellular proteins
AID  - 10.26508/lsa.202201805
DP  - 2023 Jun 01
TA  - Life Science Alliance
PG  - e202201805
VI  - 6
IP  - 6
4099  - https://www.life-science-alliance.org/content/6/6/e202201805.short
4100  - https://www.life-science-alliance.org/content/6/6/e202201805.full
SO  - Life Sci. Alliance2023 Jun 01; 6
AB  - Cellular functionality relies on a well-balanced, but highly dynamic proteome. Dysfunction of mitochondrial protein import leads to the cytosolic accumulation of mitochondrial precursor proteins which compromise cellular proteostasis and trigger a mitoprotein-induced stress response. To dissect the effects of mitochondrial dysfunction on the cellular proteome as a whole, we developed pre-post thermal proteome profiling. This multiplexed time-resolved proteome-wide thermal stability profiling approach with isobaric peptide tags in combination with a pulsed SILAC labelling elucidated dynamic proteostasis changes in several dimensions: In addition to adaptations in protein abundance, we observed rapid modulations of the thermal stability of individual cellular proteins. Different functional groups of proteins showed characteristic response patterns and reacted with group-specific kinetics, allowing the identification of functional modules that are relevant for mitoprotein-induced stress. Thus, our new pre-post thermal proteome profiling approach uncovered a complex response network that orchestrates proteome homeostasis in eukaryotic cells by time-controlled adaptations of the abundance and the conformation of proteins.