PXD062112

PXD062112 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-21 05:28:02	ID requested
⏵ 1	2025-10-28 16:55:31	announced

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;

submitter keyword: MRPS38, ribosomes, mitochondria, AURKAIP1

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

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PRIDE project URI

• PRIDE
  1. PXD062112
     1. Label: PRIDE project
     2. Name: Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease