TY - JOUR T1 - Mitochondrial dysfunction rapidly modulates the abundance and thermal stability of cellular proteins JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201805 VL - 6 IS - 6 SP - e202201805 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 Y1 - 2023/06/01 UR - https://www.life-science-alliance.org/content/6/6/e202201805.abstract N2 - 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. ER -