| First Author | Małecki JM | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 4 | Pages | 1128-1141 |
| PubMed ID | 30530489 | Mgi Jnum | J:283179 |
| Mgi Id | MGI:6277238 | Doi | 10.1074/jbc.RA118.005473 |
| Citation | Malecki JM, et al. (2018) Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase. J Biol Chem |
| abstractText | Lysine methylation is an important post-translational modification that is also present on mitochondrial proteins, but the mitochondrial lysine-specific methyltransferases (KMTs) responsible for modification are in most cases unknown. Here, we set out to determine the function of human family with sequence similarity 173 member B (FAM173B), a mitochondrial methyltransferase (MTase) reported to promote chronic pain. Using bioinformatics analyses and biochemical assays, we found that FAM173B contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria. Interestingly, CRISPR/Cas9-mediated knock-out (KO) of FAM173B in mammalian cells abrogated trimethylation of Lys-43 in ATP synthase c-subunit (ATPSc), a modification previously reported as ubiquitous among metazoans. ATPSc methylation was restored by complementing the KO cells with enzymatically active human FAM173B or with a putative FAM173B orthologue from the nematode Caenorhabditis elegans. Interestingly, lack of Lys-43 methylation caused aberrant incorporation of ATPSc into the ATP synthase complex, and resulted in decreased ATP-generating ability of the complex, as well as decreased mitochondrial respiration. In summary, we have identified FAM173B as the long-sought KMT responsible for methylation of ATPSc, a key protein in cellular ATP production, and have demonstrated functional significance of ATPSc methylation. We suggest renaming FAM173B to ATPSc-KMT (gene name ATPSCKMT). |
