PXD060404 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes |
Description | Protein misfolding is a contributor to the development of type 2 diabetes (T2D), but it is unknown whether impaired proteostasis in T2D is generalized or has special features. Here, we report a robust accumulation of misfolded proteins within the mitochondria of human pancreatic islets from patients with T2D and elucidate its impact on β cell viability. Quantitative proteomics studies of protein aggregates surprisingly reveal that islets from donors with T2D have a signature more closely resembling mitochondrial rather than ER protein misfolding. Loss of the matrix protease LONP1, a vital component of the mitochondrial proteostatic machinery whose expression is reduced in β cells of donors with T2D, yields mitochondrial protein misfolding and reduced respiratory function, ultimately leading to β cell apoptosis and hyperglycemia. Intriguingly, LONP1 gain of function ameliorates mitochondrial protein misfolding and restores human β cell survival following glucolipotoxicity via a protease-independent effect requiring LONP1-mtHSP70 chaperone activity. Thus, LONP1 promotes β cell survival and prevents hyperglycemia by facilitating mitochondrial protein folding. These observations open novel insights into the nature of proteotoxicity that promotes β cell loss during the pathogenesis of T2D that could be considered as future therapeutic targets. |
HostingRepository | PRIDE |
AnnounceDate | 2025-06-05 |
AnnouncementXML | Submission_2025-06-05_06:40:54.101.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yamei Deng |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-01-31 10:25:27 | ID requested | |
⏵ 1 | 2025-06-05 06:40:54 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Diabetes |
apoptosis |
mitochondrial protein folding |
LONP1 |
Contact List
Scott A. |
contact affiliation | Division of Metabolism, Endocriology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48105, USA |
contact email | ssol@med.umich.edu |
lab head | |
Yamei Deng |
contact affiliation | University of Michigan |
contact email | dengya@umich.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD060404
- Label: PRIDE project
- Name: LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes