Project 10:
Causes, consequences and correction of mitochondrial protein misfolding
Abstract
This project will investigate the consequences of protein misfolding and aggregation in the mitochondrial matrix and intermembrane space. A focus will be how aggregates are sensed in these compartments and how their presence is signaled to the cytosol to facilitate rebalancing of cellular proteostasis. These cascades will be explored in the context of human disease scenarios through genetic models based on patient variants. The ultimate goal is to identify putative junctions in the cellular response to mitochondrial protein aggregation that might be leveraged to promote cytoprotection over cellular demise.
Project-relevant publications
Fessler E, Krumwiede L, Jae LT (2022) DELE1 tracks perturbed protein import and processing in human mitochondria. Nat Commun. 13(1):1853.
Bie AS, Cömert C, Körner R, Corydon TJ, Palmfeldt J, Hipp MS, Hartl FU, Bross P (2020) An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. Cell Stress Chaperones. 25(3):407-416.
Fessler E, Eckl EM, Schmitt S, Mancilla IA, Meyer-Bender MF, Hanf M, Philippou-Massier J, Krebs S, Zischka H, Jae LT (2020) A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol. Nature. 579(7799):433-437.
Brockmann M, Blomen VA, Nieuwenhuis J, Stickel E, Raaben M, Bleijerveld OB, Altelaar AFM, Jae LT, Brummelkamp TR (2017) Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling. Nature. 546(7657):307-311.
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