Human HEMK1 methylates all mitochondrial release factors and is required for mitochondrial function under stress conditions

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.

We generated HEMK1 knockout HEK293 cells and analyzed their transcriptome and proteome but detected only limited effects on the global cellular transcriptome. In contrast, we observed that many mitochondrially encoded transcripts were consistently reduced. The reduction in mitochondrial transcripts may be a secondary consequence of impaired mitochondrial translation leading to mRNA destabilization.