Screening of the Arabidopsis thaliana genome revealed three potential homologues of mammalian and yeast mitochondrial DICs (dicarboxylate carriers) designated as DIC1, DIC2 and DIC3, each belonging to the mitochondrial carrier protein family. DIC1 and DIC2 are broadly expressed at comparable levels in all the tissues investigated. DIC1–DIC3 have been reported previously as uncoupling proteins, but direct transport assays with recombinant and reconstituted DIC proteins clearly demonstrate that their substrate specificity is unique to plants, showing the combined characteristics of the DIC and oxaloacetate carrier in yeast. Indeed, the Arabidopsis DICs transported a wide range of dicarboxylic acids including malate, oxaloacetate and succinate as well as phosphate, sulfate and thiosulfate at high rates, whereas 2-oxoglutarate was revealed to be a very poor substrate. The role of these plant mitochondrial DICs is discussed with respect to other known mitochondrial carrier family members including uncoupling proteins. It is proposed that plant DICs constitute the membrane component of several metabolic processes including the malate–oxaloacetate shuttle, the most important redox connection between the mitochondria and the cytosol.
Despite much study of the role of S-adenosylmethionine (SAM) in the methylation of DNA, RNA, and proteins, and as a cofactor for a wide range of biosynthetic processes, little is known concerning the intracellular transport of this essential metabolite. Screening of the Arabidopsis (Arabidopsis thaliana) genome yielded two potential homologs of yeast (Saccharomyces cerevisiae) and human SAM transporters, designated as SAMC1 and SAMC2, both of which belong to the mitochondrial carrier protein family. The SAMC1 gene is broadly expressed at the organ level, although only in specialized tissues of roots with high rates of cell division, and appears to be up-regulated in response to wounding stress, whereas the SAMC2 gene is very poorly expressed in all organs/tissues analyzed. Direct transport assays with the recombinant and reconstituted SAMC1 were utilized to demonstrate that this protein displays a very narrow substrate specificity confined to SAM and its closest analogs. Further experiments revealed that SAMC1 was able to function in uniport and exchange reactions and characterized the transporter as highly active, but sensitive to physiologically relevant concentrations of S-adenosylhomocysteine, S-adenosylcysteine, and adenosylornithine. Green fluorescent protein-based cell biological analysis demonstrated targeting of SAMC1 to mitochondria. Previous proteomic analyses identified this protein also in the chloroplast inner envelope. In keeping with these results, bioinformatics predicted dual localization for SAMC1. These findings suggest that the provision of cytosolically synthesized SAM to mitochondria and possibly also to plastids is mediated by SAMC1 according to the relative demands for this metabolite in the organelles.
Summary: We describe the identification and functional characterization of two Arabidopsis mitochondrial basic amino acid carriers (BAC), AtmBAC1 and AtmBAC2, which are related to the yeast ornithine (Orn) carrier Ort1p, also known as Arg11p. The arg11 mutant requires arginine (Arg) supplementation because it fails to export sufficient ornithine from the mitochondrion to the cytosol where it is converted to arginine. AtmBAC1 and, to a lesser extent, AtmBAC2 partially replaced the function of Ort1p in yeast arg11. The more efficient putative carrier, AtmBAC1, was expressed in E. coli, purified, and reconstituted into phospholipid vesicles, where it transported the basic l‐amino acids arginine, lysine, ornithine and histidine (in order of decreasing affinity). AtmBAC1 recognized l‐histidine whereas both yeast Ort1p and the mammalian ortholog ORNT1p do not. Also different from ORNT1p, AtmBAC1 did not transport citrulline. AtmBAC1 appeared to be more stereospecific than the yeast and mammalian ornithine carriers, exhibiting greater preference for the l‐forms of arginine, lysine and ornithine. By RT‐PCR, both AtmBAC1 and AtmBAC2 transcripts were detected in stems, leaves, flowers, siliques, and seedlings. Expression of AtmBAC1 in seedlings is consistent with its involvement in Arg breakdown in early seedling development, i.e. delivery of Arg to mitochondrial arginase. The Km (0.19 mm) for Arg uptake by AtmBAC1 was close to the value we previously determined for the saturable component of Arg uptake into intact mitochondria from soybean seedling cotyledons.
Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota—composition, intra- and inter-species relationships, metabolic functions—could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of “healthy” bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications—even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease.
1 May 2021 in Endocrine, Metabolic & Immune Disorders - Drug Targets
The current treatment and prevention of oral disorders follow a very sectoral control and procedures considering mouth and its structures as system completely independent from the rest of the body. The main therapeutic approach is carried out on just to keep the levels of oral bacteria and hygiene in an acceptable range compatible with one-way vision of oral-mouth health completely separated from a systemic microbial homeostasis (eubiosis vs dysbiosis). This can negatively impact on the diagnosis of more complex systemic disease and its progression. Dysbiosis is consequence of oral and gut microbiota unbalance with consequences, as reported in current literature, in cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. Likewise, there is the need to highlight and develop a novel philosophical approach in the treatments for oral diseases that will necessarily involve non-conventional approaches.
Cancer is a pathology that impacts in a profound manner all over the world. The election strategy against cancer often uses chemotherapy and radiotherapy, which, more often than not, can present many side effects and are not always considered reliable efficacy. By contrast, it is widely known that a diet rich in fruit and vegetables has a protective effect against cancer insurgence and development. Polyphenols are generally believed to be responsible for those beneficial actions, at least partially. In this review, we highlight the metabolic interaction between polyphenols and our metabolism and discuss their potential for anticancer prevention and therapy.