Gfm1, encoding mitochondrial elongation factor G1 (EFG1), is a nuclear gene essential for the elongation phase of mitochondrial protein synthesis [2]. This process is crucial for mitochondrial function, as it contributes to the production of proteins involved in oxidative phosphorylation (OXPHOS) pathways, which are vital for energy production in cells [2]. Genetic models, like mouse models, are valuable for studying Gfm1's role.

A Gfm1 knock-out (KO) mouse model was embryonically lethal, highlighting the gene's importance for normal development [1]. A Gfm1 knock-in (KI) mouse harboring the p.R671C missense mutation was viable. The R671C mutation led to reduced mitochondrial EFG1 protein content in different organs, partial reductions of in organello mitochondrial translation, and respiratory complex IV enzyme activity in the liver of 6-to 8-week-old Gfm1R671C/R671C mice [1]. Compound heterozygous Gfm1R671C/-mice showed more pronounced decreases in EFG1 protein, reduced mitochondrial translation rates in liver and brain, combined oxidative phosphorylation deficiency, and lower amounts of affected complexes, making them a suitable model for studying combined oxidative phosphorylation deficiency type 1 (COXPD1) [1].

In conclusion, Gfm1 is essential for mitochondrial translation and normal physiological function. The Gfm1 KO and KI mouse models have revealed its role in mitochondrial function and the development of COXPD1, providing important insights into the underlying mechanisms of this disease [1].

References:

1. Molina-Berenguer, Miguel, Vila-Julià, Ferran, Pérez-Ramos, Sandra, Torres-Torronteras, Javier, Martí, Ramon. . Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to Gfm1 mutations. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22091. doi:10.1096/fj.202100819RRR. https://pubmed.ncbi.nlm.nih.gov/34919756/

2. Ravn, Kirstine, Schönewolf-Greulich, Bitten, Hansen, Rikke M, Wibrand, Flemming, Ostergaard, Elsebet. 2015. Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations. In Molecular genetics and metabolism reports, 3, 5-10. doi:10.1016/j.ymgmr.2015.01.004. https://pubmed.ncbi.nlm.nih.gov/26937387/