Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.

Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized to mitochondria in neuroblastoma cells, where it enhances preservation of mitochondrial function. In this study, we show that aprataxin deficiency impairs mitochondrial function, independent of its role in mitochondrial DNA repair. The bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is caused by decreased expression of SDHA and genes encoding CoQ biosynthetic enzymes, in association with reductions of APE1, NRF1 and NRF2. The biochemical and molecular abnormalities in APTX-depleted cells are recapitulated by knockdown of APE1 in Hela cells and are rescued by overexpression of NRF1/2. Importantly, pharmacological upregulation of NRF1 alone by 5-aminoimidazone-4-carboxamide ribonucleotide does not rescue the phenotype, which, in contrast, is reversed by the upregulation of NRF2 by rosiglitazone. Accordingly, we propose that the lack of aprataxin causes reduction of the pathway APE1/NRF1/NRF2 and their target genes. Our findings demonstrate a critical role of APTX in transcription regulation of mitochondrial function and the pathogenesis of AOA1 via a novel pathomechanistic pathway, which may be relevant to other neurodegenerative diseases.

Co-cultivation of Beta vulgaris limits the pre-harvest colonization of foodborne pathogen (Salmonella spp.) on tomato.

Soil-borne Salmonella is associated with a large number of food-related disease outbreaks linked to pre-harvest contamination of plants (like tomato) in agricultural fields. Controlling the spread of Salmonella at field is very important in order to prevent various food-borne illnesses. One such approach involves the utilization of antimicrobial secondary metabolite of plant origin. We screened common salad vegetables for anti-Salmonella activity. Beta vulgaris root (beetroot) had very low colonization of Salmonella under in vitro conditions. We hypothesized that beetroot can be used to reclaim the soil contaminated with Salmonella. Cultivation of B. vulgaris in Salmonella treated soil brings down its CFU significantly. Since these antimicrobial effects are non-specific, a co-cultivation system of beet and tomato (a Salmonella susceptible plant) was used to analyze the effect on soil and its microbiota. The soil physicochemical properties and bacterial diversity were unaffected when tomato and beet co-cultivation was used. However, Salmonella burden on the tomato was reduced and its yield was restored. Thus, the inclusion of these crops in the crop-rotation or as a mixed/intercrop or as a bio-control crop can be a fruitful tool to reclaim the Salmonella contaminated soil.