Combined oxidative phosphorylation deficiency-1 (COXPD1) resulting from a mutation in the G elongation factor mitochondrial 1 (GFM1) gene is an autosomal recessive multisystem disorder arising from a defect in the mitochondrial oxidative phosphorylation system. Death usually appears in the first weeks or years of lifespan.
We report a male patient with ventriculomegaly diagnosed in the 8th month of pregnancy. The delivery was done by caesarean section and respiratory failure occurred immediately after birth. Hypoglycemia, lactic acidosis, elevated gamma-glutamyl transferase and hepatomegaly were confirmed. The brain MRI detected hypoplasia of the cerebellar hemispheres, dilated lateral ventricles, and markedly immature brain parenchyma. Epilepsy had been present since the third month. At 5 months of age, neurological follow-up showed his head circumference to be 37 cm, with plagiocephaly, a low hairline, a short neck, axial hypotonia and he did not adopt any developmental milestones. A genetic mutation, a missense variant in the GFM1 gene, was confirmed: c.748C > T (p.Arg250Trp) was homozygous in the GFM1 gene.
To the best of our knowledge, 28 cases of COXPD1 disease caused by mutations in the GFM1 gene have been described in the literature. COXPD1 should be considered due to symptoms and signs which begin during intrauterine life or at birth. Signs of impaired energy metabolism should indicate that the disease is in the group of metabolic encephalopathies.

Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 (COXPD1) is a recessive mitochondrial translation disorder caused by mutations in GFM1, a nuclear gene encoding mitochondrial elongation factor G1 (EFG1). Patients with COXPD1 typically present hepatoencephalopathy early after birth with rapid disease progression, and usually die within the first few weeks or years of life. We have generated two different mouse models: a Gfm1 knock-in (KI) harboring the p.R671C missense mutation, found in at least 10 patients who survived more than 1 year, and a Gfm1 knock-out (KO) model. Homozygous KO mice (Gfm1-/- ) were embryonically lethal, whereas homozygous KI (Gfm1R671C / R671C ) mice were viable and showed normal growth. R671C mutation in Gfm1 caused drastic reductions in the mitochondrial EFG1 protein content in different organs. Six- to eight-week-old Gfm1R671C / R671C mice showed partial reductions of in organello mitochondrial translation and respiratory complex IV enzyme activity in the liver. Compound heterozygous Gfm1R671C /- showed a more pronounced decrease of EFG1 protein in liver and brain mitochondria, as compared with Gfm1R671C / R671C mice. At 8 weeks of age, their mitochondrial translation rates were significantly reduced in both tissues. Additionally, Gfm1R671C /- mice showed combined oxidative phosphorylation deficiency (reduced complex I and IV enzyme activities in liver and brain), and blue native polyacrylamide gel electrophoresis analysis revealed lower amounts of both affected complexes. We conclude that the compound heterozygous Gfm1R671C /- mouse presents a clear dysfunctional molecular phenotype, showing impaired mitochondrial translation and combined respiratory chain dysfunction, making it a suitable animal model for the study of COXPD1.

While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.

Mucor circinelloides is a dimorphic fungus that is a non-pathogen strain belonging to zygomycetes. In this research, a part of hypothetical mechanism on yeast-like cell induction of M. circinelloides in CO2 atmosphere was reported from the viewpoint of gene expression. To explain the relation between the change and the expressions of some genes involved in morphological changes of the strain, these were analyzed on the filamentous and yeast cell by real-time qPCR. The compared genes were Nce103, Ras3, Cyr1, Pde, and Efg1 encoding carbonic anhydrase, GTPase, adenylate cyclase, phosphodiesterase, and elongation factor G1, respectively. In anaerobic grown yeast cell with 70%N2 + 30%CO2, the Nce103 and Ras3 gene expressions decreased to 24 h whereas that of the filamentous cell increased. However, a downstream gene of Cyr1 expression level in the yeast cell was higher than that of filamentous cell. A lower level of Pde in the yeast cell than that of the filamentous cell indicated intracellular cAMP accumulation. The actual cAMP in the yeast cell remained whereas that of the filamentous cell decreased with cultivation. The Efg1 expression level controlling hyphal elongation was suppressed in the yeast cell. The intracellular cAMP accumulation and Efg1 expression regulate hyphal elongation or yeast forming.