PXD062112 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease |
| Description | Mitochondrial acquisition was a pivotal event in eukaryotic evolution, requiring core proteins adapt to function both within the mitochondria and in the host cell. Here, we systematically profile the localization of protein isoforms generated by alternative start codon selection. We identify hundreds of pairs of differentially-localized protein isoforms, many of which affect mitochondrial targeting and are essential for mitochondrial function. The emergence of dual-localized mitochondrial protein isoforms coincides with mitochondrial acquisition during early eukaryotic evolution. We further reveal that eukaryotes use diverse mechanisms—such as leaky ribosome scanning, alternative transcription, and paralog duplication—to maintain the production dual-localized isoforms. Finally, we identify multiple isoforms that are specifically dysregulated through rare disease patient mutations and demonstrate how these mutations can help explain unique clinical presentation. Together, our findings illuminate the evolutionary and pathological relevance of alternative translation initiation, offering new insights into the molecular underpinnings of mitochondrial biology. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-10-28 |
| AnnouncementXML | Submission_2025-10-28_16:55:30.285.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD062112 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Jimmy Ly |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | TMT6plex-126 reporter+balance reagent acylated residue |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-03-21 05:28:02 | ID requested | |
| ⏵ 1 | 2025-10-28 16:55:31 | announced | |
Publication List
| Ly J, Tao YF, Di Bernardo M, Khalizeva E, Giuliano CJ, Lourido S, Fleming MD, Cheeseman IM, Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease. bioRxiv, ():(2025) [pubmed] |
| 10.1101/2025.03.27.645657; |
| 10.6019/PXD062112; |
Keyword List
| submitter keyword: MRPS38, ribosomes, mitochondria, AURKAIP1 |
Contact List
| Iain Cheeseman |
|---|
| contact affiliation | Whitehead Institute and MIT |
| contact email | icheese@wi.mit.edu |
| lab head | |
| Jimmy Ly |
|---|
| contact affiliation | PhD student |
| contact email | jimmyly@wi.mit.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD062112 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD062112
- Label: PRIDE project
- Name: Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease
