FAH domain containing protein 1 (FAHD-1) is required for mitochondrial function and locomotion activity in C. elegans

• Published in: PloS one 2015-08, Vol.10 (8), p.e0134161-e0134161
• Main Authors: Taferner, Andrea, Pircher, Haymo, Koziel, Rafal, von Grafenstein, Susanne, Baraldo, Giorgia, Palikaras, Konstantinos, Liedl, Klaus R, Tavernarakis, Nektarios, Jansen-Dürr, Pidder
• Format: Article
• Language: English
• Subjects: Aging; Animals; Bends; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Carboxy-Lyases - genetics; Carboxy-Lyases - metabolism; Cloning; Computer worms; Deactivation; Deregulation; Dopamine; Egg laying; Electron transport; Electron transport chain; Enzymes; Eukaryotes; Fatigue tests; Fumarylacetoacetase; Gene expression; Genetics; High temperature; Homology; Humans; Hydrolases - genetics; Inactivation; Life span; Locomotion; Locomotion - genetics; Locomotion - physiology; Membrane potential; Metabolism; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Molecular biology; Mutation; Nematodes; Neurosciences; Oxaloacetate decarboxylase; Oxygen; Oxygen consumption; Physical activity; Protein folding; Proteins; Serotonin; Unfolded Protein Response - genetics; Worms
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134161

The fumarylacetoacetate hydrolase (FAH) protein superfamily of metabolic enzymes comprises a diverse set of enzymatic functions, including ß-diketone hydrolases, decarboxylases, and isomerases. Of note, the FAH superfamily includes many prokaryotic members with very distinct functions that lack homologs in eukaryotes. A prokaryotic member of the FAH superfamily, referred to as Cg1458, was shown to encode a soluble oxaloacetate decarboxylase (ODx). Based on sequence homologies to Cg1458, we recently identified human FAH domain containing protein-1 (FAHD1) as the first eukaryotic oxaloacetate decarboxylase. The physiological functions of ODx in eukaryotes remain unclear. Here we have probed the function of fahd-1, the nematode homolog of FAHD1, in the context of an intact organism. We found that mutation of fahd-1 resulted in reduced brood size, a deregulation of the egg laying process and a severe locomotion deficit, characterized by a reduced frequency of body bends, reduced exploratory movements and reduced performance in an endurance exercise test. Notably, mitochondrial function was altered in the fahd-1(tm5005) mutant strain, as shown by a reduction of mitochondrial membrane potential and a reduced oxygen consumption of fahd-1(tm5005) animals. Mitochondrial dysfunction was accompanied by lifespan extension in worms grown at elevated temperature; however, unlike in mutant worms with a defect in the electron transport chain, the mitochondrial unfolded protein response was not upregulated in worms upon inactivation of fahd-1. Together these data establish a role of fahd-1 to maintain mitochondrial function and consequently physical activity in nematodes.