TY - JOUR T1 - IMiQC: a novel protein quality control compartment protecting mitochondrial functional integrity JF - bioRxiv DO - 10.1101/075127 SP - 075127 AU - Michael Bruderek AU - Witold Jaworek AU - Anne Wilkening AU - Cornelia Rüb AU - Giovanna Cenini AU - Marc Sylvester AU - Wolfgang Voos Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/14/075127.abstract N2 - Aggregation processes can cause severe perturbations of cellular homeostasis and are frequently associated with diseases. We performed a comprehensive analysis of mitochondrial quality and function in presence of misfolded, aggregation-prone polypeptides. Although we observed significant aggregate formation inside mitochondria, we observed only a minor impairment of mitochondrial function. We could show that detoxification of misfolded reporter polypeptides as well as endogenous proteins inside mitochondria takes place via their sequestration into the specific organellar deposit site Intra-Mitochondrial Protein Quality Control Compartment (IMiQC). Only minor amounts of co-aggregated proteins were associated with IMiQC and neither resolubilization nor degradation by the mitochondrial PQC system were observed. The single IMiQC aggregate deposit was not transferred to daughter cells during cell division. Detoxification of misfolded polypeptides via IMiQC formation was highly dependent on a functional mitochondrial fission machinery. We conclude that the formation of the aggregate deposit is an important mechanism to maintain full functionality of mitochondria under proteotoxic stress conditions.2D-Page2-dimensional polyacrylamide gel electrophoresis;Δψmtelectric potential across the inner mitochondrial membrane;AAamino acid;BN-PAGEblue-native polyacrylamide gel electrophoresis;DHFRdihydrofolate reductase;GFPgreen fluorescent protein;IMMinner mitochondrial membrane;IMSintermembrane space;MPPmitochondrial processing peptidase;MTSmitochondrial targeting sequence;OMMouter mitochondrial membrane;SDmstandard error of the mean;SDS-PAGEsodiumdodecylsulfate polyacrylamide gel electrophoresis;TCAtrichloroacetic acid;TOMtranslocase of the outer membrane;TIMtranslocase of the inner membrane;TMREtetramethylrhodamine ethyl ester.2D-Page2-dimensional polyacrylamide gel electrophoresis;Δψmtelectric potential across the inner mitochondrial membrane;AAamino acid;BN-PAGEblue-native polyacrylamide gel electrophoresis;DHFRdihydrofolate reductase;GFPgreen fluorescent protein;IMMinner mitochondrial membrane;IMSintermembrane space;MPPmitochondrial processing peptidase;MTSmitochondrial targeting sequence;OMMouter mitochondrial membrane;SDmstandard error of the mean;SDS-PAGEsodiumdodecylsulfate polyacrylamide gel electrophoresis;TCAtrichloroacetic acid;TOMtranslocase of the outer membrane;TIMtranslocase of the inner membrane;TMREtetramethylrhodamine ethyl ester. ER -