METTL17, also known as methyltransferase-like 17, is a mitochondrial protein. It is essential for mitochondrial function, acting as a regulator of mitochondrial translation. It is involved in pathways related to ferroptosis, a form of regulated cell death, and is associated with mitochondrial ribosome assembly [1,2,3,4]. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in further elucidating its functions.

In colorectal cancer cells, depletion of METTL17 sensitizes cells to ferroptosis, impairs cell proliferation, migration, invasion, and tumor growth. Mechanistically, its inhibition reduces mitochondrial RNA methylation, leading to impaired translation of mitochondrial protein-coding genes [1]. In Friedreich's ataxia-related studies, depletion of frataxin led to a decrease in METTL17 and impaired mitochondrial translation. Overexpression of METTL17 rescued mitochondrial translation and bioenergetic defects in frataxin-depleted cells [2]. In mouse embryonic stem cells, loss of Mettl17 affects the stability of 12S mitochondrial ribosomal RNA and associated proteins, and leads to impaired translation of mitochondrial protein-coding genes, changing mitochondrial oxidative phosphorylation and cellular metabolome [3].

In summary, METTL17 plays a crucial role in mitochondrial translation and function. Through model-based research, especially KO/CKO mouse models, its significance in diseases like colorectal cancer and Friedreich's ataxia has been revealed. These studies help understand the underlying mechanisms of these diseases and may provide potential therapeutic targets [1,2].

References:

1. Li, Hao, Yu, Kailun, Hu, Huilong, Zhang, Jianhui, Zhang, Yongyou. 2024. METTL17 coordinates ferroptosis and tumorigenesis by regulating mitochondrial translation in colorectal cancer. In Redox biology, 71, 103087. doi:10.1016/j.redox.2024.103087. https://pubmed.ncbi.nlm.nih.gov/38377789/

2. Ast, Tslil, Itoh, Yuzuru, Sadre, Shayan, Amunts, Alexey, Mootha, Vamsi K. 2024. METTL17 is an Fe-S cluster checkpoint for mitochondrial translation. In Molecular cell, 84, 359-374.e8. doi:10.1016/j.molcel.2023.12.016. https://pubmed.ncbi.nlm.nih.gov/38199006/

3. Shi, Zhennan, Xu, Siyuan, Xing, Shenghui, Hu, Zeping, Lan, Fei. 2019. Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 13040-13050. doi:10.1096/fj.201901331R. https://pubmed.ncbi.nlm.nih.gov/31487196/

4. Mashkovskaia, A V, Mariasina, S S, Serebryakova, M V, Dontsova, O A, Sergiev, P V. . Testing a Hypothesis of 12S rRNA Methylation by Putative METTL17 Methyltransferase. In Acta naturae, 15, 75-82. doi:10.32607/actanaturae.25441. https://pubmed.ncbi.nlm.nih.gov/38234605/