Moonlighting Arabidopsis molybdate transporter 2 family and GSH-complex formation facilitate molybdenum homeostasis.

Molybdenum (Mo) as essential micronutrient for plants, acts as active component of molybdenum cofactor (Moco). Core metabolic processes like nitrate assimilation or abscisic-acid biosynthesis rely on Moco-dependent enzymes. Although a family of molybdate transport proteins (MOT1) is known to date in Arabidopsis, molybdate homeostasis remained unclear. Here we report a second family of molybdate transporters (MOT2) playing key roles in molybdate distribution and usage. KO phenotype-analyses, cellular and organ-specific localization, and connection to Moco-biosynthesis enzymes via protein-protein interaction suggest involvement in cellular import of molybdate in leaves and reproductive organs. Furthermore, we detected a glutathione-molybdate complex, which reveals how vacuolar storage is maintained. A putative Golgi S-adenosyl-methionine transport function was reported recently for the MOT2-family. Here, we propose a moonlighting function, since clear evidence of molybdate transport was found in a yeast-system. Our characterization of the MOT2-family and the detection of a glutathione-molybdate complex unveil the plant-wide way of molybdate.

Adverse effects of St. John's Wort: a systematic review.

OBJECTIVE: To obtain an overview of the available clinical evidence on safety and tolerability of hypericum extracts, we reviewed (1) dropout rates and adverse effects in double-blind randomized trials comparing hypericum extracts and placebo or synthetic standard antidepressants; (2) dropout rates and adverse effects in large-scale observational studies; and (3) adverse effects reported in published cases and to public drug surveillance agencies. METHOD: Data on dropout rates and adverse effects were extracted from double-blind randomized trials of hypericum monopreparations collected for a Cochrane review (last search July 2003) and from a PubMed search (text word hypericum; search dates 1998-January 2003). Similar data were extracted from uncontrolled observational studies including at least 100 patients identified through a PubMed search (search term hypericum NOT animal, last update May 2003), contacts with manufacturers, and screening of review articles. Case reports and case series on adverse events associated with hypericum products were identified through a MEDLINE search (1966-November 2002; search term: hypericum AND [adverse effects OR interaction]) and a PubMed search (February 2003) and were collected from 5 public drug surveillance agencies (data through May 2001). All database searches were conducted as English and non-English language searches. RESULTS: Data from 35 double-blind randomized trials showed that dropout and adverse effects rates in patients receiving hypericum extracts were similar to placebo, lower than with older antidepressants, and slightly lower than with selective serotonin reuptake inhibitors. Dropout rates due to adverse effects in 17 observational studies including 35,562 patients ranged from 0% to 5.7%; interactions or serious adverse effects were not reported in any study. Published cases and cases reported to drug surveillance agencies suggest that interactions with a variety of drugs (particularly cyclosporine in transplant patients) are the most relevant adverse effects of hypericum extracts. CONCLUSIONS: The available evidence suggests that hypericum extracts are well tolerated and safe if taken under control of a physician who is aware of potentially relevant risks in specific circumstances.