PXD080370

PXD080370 is an original dataset announced via ProteomeXchange.

Title	Human HEMK1 methylates all mitochondrial release factors and is required for mitochondrial function under stress conditions
Description	HEMK1 is the mitochondrial homolog of HEMK2, the enzyme that methylates the conserved glutamine in the GGQ loop of eukaryotic translation termination factor eRF1. Previous work reported altered GGQ-loop glutamine methylation of mitochondrial release factors (MRF) after HEMK1 deletion, but direct biochemical evidence for HEMK1 catalytic activity and the functional consequences of MRF methylation for mitochondrial translation and physiology remained unclear. Here, we show that HEMK1 methylates all four human MRFs, with MTRF1L being the preferred substrate, consistent with MTRF1L’s reported role as the main stop-codon-dependent mitochondrial termination factor. We generated HEMK1 knockout HEK293 cells and analyzed their transcriptome and proteome, but detected only limited effects on the global level. In contrast, we observed that many mitochondrially encoded transcripts and proteins were consistently reduced. This decrease was generally stronger at the protein than at the transcript level, supporting a direct role of HEMK1 in mitochondrial translation. The accompanying reduction in mitochondrial transcripts may be a secondary consequence of impaired mitochondrial translation leading to mRNA destabilization via mRNA quality control. HEMK1 knockout clones showed increased sensitivity to mitochondrial stress, including elevated populations with low mitochondrial inner membrane potential and signs of apoptosis. These data indicate that loss of HEMK1 causes a latent mitochondrial defect that is tolerated under standard culture conditions but becomes apparent during mitochondrial or metabolic stress.
HostingRepository	PRIDE
AnnounceDate	2026-07-03
AnnouncementXML	Submission_2026-07-03_02:41:47.684.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Franziska Traube
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-30 04:50:41	ID requested
⏵ 1	2026-07-03 02:41:48	announced

Dataset with its publication pending

submitter keyword: HEMK1

Protein glutamine methyltransferase

Protein glutamine methylation

Translation termination factor

Mitochondrial translation

GGQ loop methylation

Franziska Traube
contact affiliation	University of Stuttgart, Institute of Biochemistry
contact email	franziska.traube@ibc.uni-stuttgart.de
lab head
Franziska Traube
contact affiliation	IBTB - University of Stuttgart
contact email	franziska.traube@cup.lmu.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD080370
     1. Label: PRIDE project
     2. Name: Human HEMK1 methylates all mitochondrial release factors and is required for mitochondrial function under stress conditions