FAH domain containing protein 1 (FAHD-1) is required for mitochondrial function and locomotion activity in C. elegans.
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.
Institute for Biomedical Aging Research and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Andrea
A
Taferner
Institute for Biomedical Aging Research and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Haymo
H
Pircher
Institute for Biomedical Aging Research and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Rafal
R
Koziel
Institute for General, Inorganic and Theoretical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
Susanne
S
von Grafenstein
Institute for Biomedical Aging Research and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Giorgia
G
Baraldo
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece; Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Konstantinos
K
Palikaras
Institute for General, Inorganic and Theoretical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
Klaus R
KR
Liedl
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece; Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Nektarios
N
Tavernarakis
Institute for Biomedical Aging Research and Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Pidder
P
Jansen-Dürr
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002262:Carboxy-Lyases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D056811:Unfolded Protein Response / Q000235:genetics
C000607392:FAHD1 protein, human; D006867:Hydrolases; D002262:Carboxy-Lyases; C021916:oxaloacetate decarboxylase