Silencing of FAD synthase gene in Caenorhabditis elegans upsets protein homeostasis and impacts on complex behavioral patterns

Liuzzi, Vania C.; Giancaspero, Teresa Anna; Gianazza, Elisabetta; Banfi, Cristina; Barile, Maria; Giorgi, Carla De

doi:10.1016/j.bbagen.2012.01.012

Cited by 17 publications

(45 citation statements)

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“…RFT-2, expressed in the intestine in C. elegans, is a homolog of the riboflavin transporter three that is required for VB2 uptake (Biswas et al, 2013; Gandhimathi et al, 2015). FLAD-1 is a FAD synthase that catalyzes the last step of FAD biosynthesis (Liuzzi et al, 2012). NPRL-3 represses TORC1 activity (Zhu et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

“…We then further analyzed the functional relationship between FAD and TORC1 by decreasing FAD production through RNAi of a FAD synthetase gene ( flad-1 ) and a riboflavin transporter gene ( rft-2) (Biswas et al, 2013; Gandhimathi et al, 2015; Liuzzi et al, 2012) (Figure 5A). Protease activity was dramatically reduced in both RNAi-treated strains and the activity was recovered in nprl-3(lf) mutants (Figure 5E,F,H and I).…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of flavins from worms was carried out as described (Liuzzi et al, 2012). In brief, worms were harvested, washed in M9 buffer, suspended in lysis buffer (10 mM Tris-HCl PH8.0, 25 mM NaCl, 1 mM EDTA, 1 X protease inhibitor) and lysed by sonication.…”

Section: Methodsmentioning

confidence: 99%

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A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

Kniazeva

Han

2017

eLife

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To survive challenging environments, animals acquired the ability to evaluate food quality in the intestine and respond to nutrient deficiencies with changes in food-response behavior, metabolism and development. However, the regulatory mechanisms underlying intestinal sensing of specific nutrients, especially micronutrients such as vitamins, and the connections to downstream physiological responses in animals remain underexplored. We have established a system to analyze the intestinal response to vitamin B2 (VB2) deficiency in Caenorhabditis elegans, and demonstrated that VB2 level critically impacts food uptake and foraging behavior by regulating specific protease gene expression and intestinal protease activity. We show that this impact is mediated by TORC1 signaling through reading the FAD-dependent ATP level. Thus, our study in live animals uncovers a VB2-sensing/response pathway that regulates food-uptake, a mechanism by which a common signaling pathway translates a specific nutrient signal into physiological activities, and the importance of gut microbiota in supplying micronutrients to animals.DOI: http://dx.doi.org/10.7554/eLife.26243.001

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

Kniazeva

Han

2017

eLife

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“…ATP content was measured fluorometrically in cellular lysates by using the ATP Detecting System, essentially as in [30]. NADPH formation, which corresponds to ATP content (with a 1 : 1 stoichiometry), was followed with excitation wavelength at 340 nm and emission wavelength at 456 nm.…”

Section: Methodsmentioning

confidence: 99%

Alteration of ROS Homeostasis and Decreased Lifespan inS. cerevisiaeElicited by Deletion of the Mitochondrial TranslocatorFLX1

Dipalo

Miccolis

Boles

et al. 2014

BioMed Research International

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This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the flx1Δ strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the flx1Δ strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts.

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“…The percentage of disembarkation was calculated based on the total number of nematodes that disembarked from an insect and nematodes remaining on the insect. To test for possible bacterial disembarkation cues, a 3-cm plate containing nematode growth medium (NGM) (Liuzzi et al, 2012) with a fresh E. coli OP50 lawn was also placed in the stainless steel pipe in the plastic cup (Fig. 1A).…”

Section: Nematodes and Insectsmentioning

confidence: 99%

Conditions for disembarkation of Caenorhabditis japonica from its carrier insect Parastrachia japonensis

Okumura

Tanaka

Yoshiga

2013

Japanese Journal of Nematology

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Silencing of FAD synthase gene in Caenorhabditis elegans upsets protein homeostasis and impacts on complex behavioral patterns

Cited by 17 publications

References 58 publications

A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

Alteration of ROS Homeostasis and Decreased Lifespan inS. cerevisiaeElicited by Deletion of the Mitochondrial TranslocatorFLX1

Conditions for disembarkation of Caenorhabditis japonica from its carrier insect Parastrachia japonensis

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