The 22 mitochondrially encoded tRNAs (mt-tRNAs) act as crucial intermediaries between the mRNAs transcribed from mtDNA and the 13 subunits of OXPHOS that they encode. As with all known tRNAs, they are required to undergo numerous post-transcriptional nucleotide modifications prior to becoming active elements in protein translation in order to ensure efficiency and stringent accuracy. Mitochondrial tRNA processing and modifying enzymes represent an expanding group of mitochondrial disease-causing factors.4 Recent research describes mitochondrial dysfunction resulting from mutations in genes encoding the tRNA processing enzymes HSD10 (also known as MRPP2 [MIM: 300256])5 and ELAC2 (MIM: 605367),6 as well as tRNA modifiers, including PUS1 (MIM: 608109),7 TRIT1,8 TRMU (also known as MTU1 [MIM: 610230]),9 TRNT1 (MIM: 612907),10,11 MTO1 (MIM: 614667),12 and GTPBP3 (MIM: 608536).13 Furthermore, primary mtDNA mutations in mt-tRNA genes, which are a frequent cause of human respiratory-chain deficiencies, can also affect mt-tRNA modification.14–16