RRC ID 53425
著者 Taferner A, Pircher H, Koziel R, von Grafenstein S, Baraldo G, Palikaras K, Liedl KR, Tavernarakis N, Jansen-Dürr P.
タイトル FAH domain containing protein 1 (FAHD-1) is required for mitochondrial function and locomotion activity in C. elegans.
ジャーナル PLoS One
Abstract 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.
巻・号 10(8)
ページ e0134161
公開日 2015-1-1
DOI 10.1371/journal.pone.0134161
PII PONE-D-15-13960
PMID 26266933
PMC PMC4534308
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Carboxy-Lyases / genetics* Carboxy-Lyases / metabolism Humans Hydrolases / genetics* Locomotion / genetics Locomotion / physiology* Mitochondria / genetics* Mitochondria / metabolism Mutation Unfolded Protein Response / genetics
IF 2.74
引用数 8
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