Methyltransferase-like protein 17 (METTL17) (METTL17)

Methyltransferase-like protein 17 (METTL17) is a mitochondrial protein that functions as a critical assembly factor for the mitochondrial small ribosomal subunit (mt-SSU) and as a methyltransferase for mitochondrial RNA (mt-RNA). It is essential for maintaining mitochondrial translation and oxidative phosphorylation (OxPhos) by ensuring the proper modification and stability of 12S rRNA. Recent research has highlighted METTL17 as a metabolic checkpoint that coordinates mitochondrial function with iron-sulfur (Fe-S) cluster availability, as it requires an Fe-S cluster for its own stability. In disease contexts, METTL17 is frequently upregulated in cancers such as colorectal cancer (CRC) and acute myeloid leukemia (AML), where it promotes tumor cell survival and resistance to ferroptosis. Consequently, METTL17 is being investigated as a therapeutic target; its inhibition via experimental methods like siRNA has been shown to eradicate leukemia stem cells and sensitize CRC cells to iron-dependent cell death. While no small-molecule inhibitors are currently in clinical use, METTL17 represents a promising target for addressing metabolic vulnerabilities in various malignancies. Additionally, its depletion is linked to the pathogenesis of Friedreich's ataxia, suggesting a broader role in mitochondrial homeostasis.

Other names

METT11D1RSM22False p73 target gene protein 1Ribosome assembly protein METTL17, mitochondrial

Inhibition of mitochondrial RNA methylation and ribosome assembly, leading to impaired mitochondrial translation and oxidative phosphorylation.