Cystinosis, an inherited disease caused by a defect in the lysosomal cystine transporter (CTNS), is characterized by renal proximal tubular dysfunction. Adenosine triphosphate (ATP) depletion appears to be a key event in the pathophysiology of the disease, even though the manner in which ATP depletion occurs is still a puzzle. We present a model that explains how a futile cycle that is generated between two ATP-utilizing enzymes of the 𝛾-glutamyl cycle leads to ATP depletion. The enzyme 𝛾-glutamyl cysteine synthetase (𝛾-GCS), in the absence of cysteine, forms 5-oxoproline (instead of the normal substrate, 𝛾-glutamyl cysteine) and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model of cystinosis, where renal failure is not observed.

The adenine biosynthetic mutants ade1 and ade2 of Saccharomyces cerevisiae accumulate a characteristic redpigment in their vacuoles under adenine limiting conditions. This red pigmentation phenotype, widely used in avariety of genetic screens and assays, is the end product of a glutathione-mediated detoxification pathway,where the glutathione conjugates are transported into the vacuole. The glutathione conjugation step, however,has still remained unsolved. We show here, following a detailed analysis of all the members of the thioredoxinfoldsuperfamily, the involvement of the monothiol glutaredoxin GRX4 as essential for pigmentation. GRX4plays multiple roles in the cell, and we show that the role in ade pigmentation does not derive from itsregulatory role of the iron transcription factor, Aft1p, but a newly identified GST activity of the protein that wecould demonstrate using purified Grx4p. Further, we demonstrate that the GRX domain of GRX4 and its activesite cysteine C171 is critical for this activity. The findings thus solve a decades old enigma on a critical step inthe formation of this red pigmentation.

Crop improvement is a continuous effort, since some 10,000 years ago when primitive man made the transitionfrom hunting and foraging to domestication and crop cultivation. Since then, man-made interventions havechanged the entire scenario of crop evolution, by means of genetic alterations of plants and animals made tosatisfy man’s needs. The process of domestication has led to dramatic changes in their appearance, quality andproductivity that have contributed substantially to global food security. The tremendous decline in cultivableland, freshwater, and increasing risk of biotic and abiotic stress demand immediate attention on cropimprovement to cope with the higher demand of ~40% of the food by 2020. Therefore, plant genetic variationplays a key role in plant breeding for its improvement. Most of the genetic variations useful for cropimprovement have been deposited and maintained in seed gene banks across the world; they need to be broughtinto the mainstream of breeding lines. Recent advances and progress made in molecular markers have beensubstantial tools for deeper insights of genetics, and greatly complemented breeding strategies. Integration of thenext-generation sequencing (NGS) technologies with precise phenotyping, association mapping, proteome andmetabolome studies has increased the chances of finding candidate genes and their allelic variants controlling atrait of interest. Further, these functional markers (FMMs), genotype-by-sequencing and association mappingmethodologies have opened new avenues for identification of novel genetic resources (lines) that can facilitateaccelerated crop breeding programs for increased yield, high nutritional quality, and tolerance to a variety ofabiotic and biotic stresses. The details of popular molecular markers, advancement in the technologies andstrategies for crop diversity studies and their application in crop breeding programs are presented here.