The molecular mechanism of aluminum toxicity in biological systems remains poorly understood. In this study, the relationship between aluminum and intracellular calcium was investigated in Saccharomyces cerevisiae model cells. Genetic analysis demonstrated that deletion mutants of plasma membrane calcium transport cch1Δ and mid1Δ, as well as the Golgi calcium pump deletion mutant pmr1Δ, increased the sensitivity to aluminum, while their sensibility could be compensated by exogenous calcium. Strains of cch1Δ and mid1Δ treated by Ca2+ chelator EGTA was more sensitive to aluminum compared with BY4741 and pmc1Δ. Further ICP-AES analysis showed that calcium uptake through both CCH1 and MID1 did not detoxify by inhibiting aluminum absorption. Meanwhile, aluminum treatment did not change the intracellular calcium uptake in cch1Δ, and mid1Δ, although it increased the mRNA levels of CCH1 or MID1 in all tested strains. It suggests that the increase in intracellular calcium induced by aluminum is CCH1 and MID1-dependent. Subsequently, the intracellular calcineurin-CRZ1 pathway was activated under aluminum stress to promote the expression of CCH1, MID1 and PMR1. Notably, overexpression of PMR1 significantly reduced intracellular aluminum levels and enhanced aluminum tolerance in both wild-type and mutant strains (cch1Δ, cnb1Δ, and crz1Δ). Furthermore, another vesicle transport deletion mutant gos1Δ or the strains (WT and gos1Δ) treated by BFA (a vesicle transport inhibitor) showed enhanced sensitivity to aluminum stress. However, exogenous calcium and/or PMR1 overexpression could reverse this sensitivity. Altogether, increasing intracellular calcium serves as a protective response to aluminum stress. The calcium-related signaling, particularly PMR1-mediated vesicle transport, plays a crucial role in aluminum detoxification.

• PMID: 41427904
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Journal Article

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Yu R, Gan Z, Chen R, Shen Y, Deng Y, Huang Z

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