PXD032011 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Orphan precursor proteins and ROS activate the mitochondrial UPR_Redox proteomics |
Description | The mitochondrial unfolded protein response (UPRmt) safeguards mitochondria from proteotoxic damage by activating a dedicated transcriptional response in the nucleus to restore proteostasis. How the mitochondrial protein misfolding information is signalled to the nucleus as part of the human UPRmt remains unclear. Here, we showed that UPRmt signalling is carried out by the co-occurrence of two individual signals – ROS production in mitochondria and accumulation of orphan mitochondrial proteins in the cytosol. Combining proteomics and genetic approaches, we identified that mitochondrial protein misfolding caused the release of ROS into the intermembrane space (IMS), which was essential for UPRmt signalling. ROS released from mitochondria oxidized the cytosolic HSP40 protein DNAJA1 to enhance recruitment of cytosolic HSP70 to orphan mitochondrial proteins that accumulated in parallel in the cytosol due to mitochondrial import defect. This recruitment leads to the release of HSF1 from HSP70 and its subsequent translocation to the nucleus to activate transcription of UPRmt related genes. Strikingly, we found that combining ROS and the accumulation of orphan mitochondrial proteins in the cytosol was sufficient and necessary to activate the UPRmt. Our findings reveal that monitoring of ROS and orphan mitochondrial proteins in cytosol allows an elegant surveillance to control the UPRmt via HSF1 activation in human cells. These observations reveal a novel link between mitochondrial and cytosolic proteostasis and provide molecular insight into UPRmt signalling. |
HostingRepository | PRIDE |
AnnounceDate | 2023-05-19 |
AnnouncementXML | Submission_2023-05-19_05:44:22.233.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ReymondSutandy |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-02 09:46:25 | ID requested | |
⏵ 1 | 2023-05-19 05:44:22 | announced | |
2 | 2023-11-14 08:08:33 | announced | 2023-11-14: Updated project metadata. |
Publication List
Keyword List
submitter keyword: UPRmt, proteomics, iodoTMT, ROS, mitochondria,redox |
Contact List
ChristianMünch |
contact affiliation | Institute of Biochemistry II Goethe University Frankfurt – Medical School University Hospital Germany |
contact email | ch.muench@em.uni-frankfurt.de |
lab head | |
ReymondSutandy |
contact affiliation | Institute of Biochemistry II, Frankfurt |
contact email | sutandy@med.uni-frankfurt.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032011
- Label: PRIDE project
- Name: Orphan precursor proteins and ROS activate the mitochondrial UPR_Redox proteomics