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This paper aims at analysing the synthesis of flavonoids, their import and export in plant cell compartments, as well as their involvement in the response to stress, with particular reference to grapevine (Vitis vinifera L.). A multidrug and toxic compound extrusion (MATE) as well as ABC transporters have been demonstrated in the tonoplast of grape berry, where they perform a flavonoid transport. The involvement of a glutathione S-transferase (GST) gene has also been inferred. Recently, a putative flavonoid carrier, similar to mammalian bilitranslocase (BTL), has been identified in both grape berry skin and pulp. In skin the pattern of BTL expression increases from véraison to harvest, while in the pulp its expression reaches the maximum at the early ripening stage. Moreover, the presence of BTL in vascular bundles suggests its participation in long distance transport of flavonoids. In addition, the presence of a vesicular trafficking in plants responsible for flavonoid transport is discussed. Finally, the involvement of flavonoids in the response to stress is described.

Fruits and vegetables are rich in flavonoids, and ample epidemiological data show that diets rich in fruits and vegetables confer protection against cardiovascular, neurodegenerative and inflammatory diseases, and cancer. However, flavonoid bioavailability is reportedly very low in mammals and the molecular mechanisms of their action are still poorly known. This review focuses on membrane transport of flavonoids, a critical determinant of their bioavailability. Cellular influx and efflux transporters are reviewed for their involvement in the absorption of flavonoids from the gastro-intestinal tract and their subsequent tissue distribution. A focus on the mammalian bilirubin transporter bilitranslocase (TCDB 2.A.65.1.1) provides further insight into flavonoid bioavailability and its relationship with plasma bilirubin (an endogenous antioxidant). The general function of bilitranslocase as a flavonoid membrane transporter is further demonstrated by the occurrence of a plant homologue in organs (petals, berries) where flavonoid biosynthesis is most active. Bilitranslocase appears associated with sub-cellular membrane compartments and operates as a flavonoid membrane transporter.

BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes. In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria. The effect of the peptide was synergistic with that of Ca 2؉ and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore. The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release. We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ. Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.Mitochondria are the focus of intense research as major integrators and regulators of cell death pathways (7,8,10,15). Release of death-promoting factors by mitochondria has been reported as a regulatory event in apoptotic death mediated by different signals (20,35,37,39). Mitochondrial dysfunction may also cause necrotic death, and the role played by mitochondria has been well documented in several experimental systems (1,21,23,40). The central role of mitochondria as integrators of the death effector mechanisms is suggested by the fact that several signals derived either from external stimuli or from the cytosol or nucleus converge on mitochondria to trigger cell death (8).The human antimicrobial peptide hystatin 5 was recently added to the number of toxic agents that act through mitochondria. This molecule is cytotoxic to Candida albicans in a manner dependent on functionally active mitochondria, as inhibition of respiration protects the cells from its toxicity (16). Likewise, de-energized human cell lines are protected from the cytotoxic effects of other antimicrobial peptides such as the human defensins (25, 26) and the bovine BMAP-28, a cationic peptide of the cathelicidin family (34,36,45). The latter agent causes membrane permeabilization and death of activated human lymphocytes and tumor cells (34). The cytotoxic activity has been related to the structural features of the peptide, which consists of a cationic N-terminal sequence predicted to assume an amphipathic ␣-helical conformation (residues 1 to 18) and a C-terminal hydrophobic tail (residues 19 to 27). The C-terminal sequence seems to be crucial for the cytotoxic activity, as a great reduction of this effect is observed with the synthetic analogue BMAP-28(1-18) comprising the 18 N-terminal residues (36). A second requirement for cytotoxicity is an active metabolism of the target cells, as BMAP-28 is ineffective in nonrespiring cells (34).In view of these observations, we have investigated whether mitochondria are targets of the peptide itself and/or mediators of i...

Flavonoids are a group of secondary metabolites widely distributed in plants that represent a huge portion of the soluble phenolics present in grapevine (Vitis vinifera L.). These compounds play different physiological roles and are often involved in protection against biotic and abiotic stress. Even if the flavonoid biosynthetic pathways have been largely characterized, the mechanisms of their transport and accumulation in cell wall and vacuole are still not completely understood. This review analyses the known mechanisms of flavonoid uptake and accumulation in grapevine, with reference to the transport models and membrane carrier proteins described in other plant species. The effect of different environmental factors on flavonoid biosynthesis and transporters is also discussed.