A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function

Abstract

Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD+-dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.

ROS-induced translational regulation—through spatiotemporal differences in codon recognition—is a key driver of brown adipogenesis

“…Interestingly, ELP3 has been found to localize to mitochondria in HeLa cells 34 and Toxoplasma gondii 35 . It was also recently reported that a novel splice variant of ELP3 is localized to the mitochondrial matrix, where it modifies mitochondrial tRNAs, and in so doing, protects the tRNAs from degradation 36 .…”

“…Interestingly, ELP3 has been found to localize to mitochondria in HeLa cells 34 and Toxoplasma gondii 35 . It was also recently reported that a novel splice variant of ELP3 is localized to the mitochondrial matrix, where it modifies mitochondrial tRNAs, and in so doing, protects the tRNAs from degradation 36 . If these mechanisms are also in play during brown adipogenesis, they will add a further dimension to how translational changes might be localized and effected.…”