Biotin deficiency decreases life span and fertility but increases stress resistance in Drosophila melanogaster

Abstract

Biotin deficiency is associated with fetal malformations and activation of cell survival pathways in mammals. In this study we determined whether biotin status affects life span, stress resistance, and fertility in the fruit fly Drosophila melanogaster. Male and female flies of the Canton-S strain had free access to diets containing 6.0 (control), 4.8, 2.5, or 0 pmol biotin/100 mg. Biotin concentrations in diets correlated with activities of biotin-dependent propionyl-CoA carboxylase and biotin concentrations in fly homogenates, but not with biotinylation of histones (DNA-binding proteins). Propionyl-CoA carboxylase activities and biotin concentrations were lower in males than in females fed diets low in biotin. The life span of biotin-deficient males and females was up to 30% shorter compared to biotinsufficient controls. Exposure to oxidative stress reversed the effects of biotin status on survival in male flies: survival times increased by 40% in biotin-deficient males compared to biotin-sufficient controls. Biotin status did not affect survival of females exposed to oxidative stress. Exposure of flies to cold, heat, and oxidative stress was associated with mobilization of biotin from yet unknown sources. Biotin deficiency decreased fertility of flies. When biotin-deficient males and females were mated, the hatching rate (larvae hatched per egg) decreased by about 28% compared to biotin-2 sufficient controls. These findings are consistent with the hypothesis that biotin affects life span, stress resistance, and fertility in fruit flies.

Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster

“…When flies were fed diets containing 1% dried grape leaves there was an increase in biotinylated ACC, MCC, PCC, and PC in males and an increase in biointylated PC in females. The absence of detectable ACC1, ACC2, MCC, and PCC was previously reported in female flies [17]. This was accompanied by an increase in HLCS protein (Fig.…”

“…Triacylglycerols in the heat-inactivated (5 min at 70°C) extracts were incubated with Infinity Triglycerides solution (Thermo Scentific) at 37°C for 35 min and quantified colorimetrically (540 nm) using triolein as standard [16]. Biotinylated carboxylases were isolated from fly homogenates as described previously [17] and analyzed by streptavidin blot analysis.…”

Enrichment of meiotic recombination hotspot sequences by avidin capture technology

“…Importantly, de-repression of LTRs provides a mechanistic rationale for linking biotin deficiency with aberrant meiosis, because the majority of mammalian LTRs contain the 13-bp consensus motif located in hotspots for meiotic recombination (Myers et al, 2008). This theory is also consistent with our observation that biotin deficiency lowers fertility in Drosophila (Landenberger et al, 2004). …”

“…The interactions between HLCS and EHMT1 are strengthened by HLCS-dependent biotinylation of K161 in EHMT1. Both biotin depletion and HLCS knockdown decrease biotinylation marks and H3K9me marks to a similar extent, and cause severe phenotypes such as short life span (Landenberger et al, 2004), low fertility (Landenberger et al, 2004; Camporeale et al, 2006), and low resistance to heat stress in Drosophila melanogaster (Camporeale et al, 2006), and de-repression of LTRs in humans, mammalian cell lines, and in Drosophila (Chew et al, 2008; Pestinger et al, 2011; Rios-Avila et al, 2012). Importantly, de-repression of LTRs provides a mechanistic rationale for linking biotin deficiency with aberrant meiosis, because the majority of mammalian LTRs contain the 13-bp consensus motif located in hotspots for meiotic recombination (Myers et al, 2008).…”

Biotin deficiency stimulates survival pathways in human lymphoma cells exposed to antineoplastic drugs

“…For example, biotin deficiency is associated with increased survival of the fruit fly Drosophila melanogaster if exposed to oxidative stress [38]. Likewise, evidence has been provided that biotin deficiency is associated with increased survival of lymphoma cells cultured in serum-free medium or treated with tumor necrosis factor-a; p50 and p65 are likely to play a role in this process [8].…”