**Author details**

manifested at several levels [41]. For example, high Mn2+ is controlled by calcineurin/Crz1pregulated Pmr1p and Pun1p [100]. Importantly, the tolerance of yeast cells to Mn2+ is related to both Pmr1p and Vcx1p [41, 64, 65, 101] two determinants of maintaining low [Ca2+]cyt by transporting the ions to the vacuole and Golgi/ER, respectively [60–63]. The Ca2+-dependent response to Mn2+ surplus seems to be induced not by external Mn2+, but by the cations accumulated inside the cell. For example, it was found that internal Mn2+ can be redistributed by

Cd2+-exposure, and the cells die. B. Cells lacking Cch1p (but not Mid1p) exhibit lower elevations in Cu2+-induced [Ca2+]

and are more tolerant to Cu2+ stress. C. Cells lacking Yvc1p (knock-out mutant *yvc1Δ*) exhibit very low elevations in Cu2+-

cyt and adapt easily to Cu2+ stress [24]. The cell behavior described in A-C is similar to the Ca2+-mediated

cyt elevations mediate cell adaptation or cell death under Cu2+ stress. A. In normal (WT,

cyt elevations as Ca2+ enters via Cch1p/Mid1p channel or is released from the

cyt are not rapidly restored as in the case of

cyt changes may be indirectly mediated by the

(D).

cyt

Fe2+ toxicity can be the result of direct ionic effect, but the indirect effect of catalyzing Fenton reactions, in which highly reactive oxygen species arise, represents the main concern raised

calcium-stimulated vesicle trafficking [102].

**4.4. Fe2+**

**Figure 6.** Cu2+-induced [Ca2+]

32 Calcium and Signal Transduction

induced [Ca2+]

wild type) cells, surplus Cu2+ induces [Ca2+]

vacuole via Yvc1p, in a positive feed-back. The normal low levels of [Ca2+]

response to oxidative stress [18], suggesting that the Cu2+-induced [Ca2+]

formation of reactive oxygen species during copper shuffling between oxidative states Cu2+-Cu<sup>+</sup>

Ileana Cornelia Farcasanu\*, Claudia Valentina Popa and Lavinia Liliana Ruta

\*Address all correspondence to: ileana.farcasanu@chimie.unibuc.ro

Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Bucharest, Romania
