PKA-dependent remodeling of trehalose metabolism under boric acid stress

Trehalose metabolism is essential for stress protection and metabolic adaptation in Saccharomyces cerevisiae. Boric acid, a micronutrient that becomes toxic at elevated levels, is known to disrupt metabolic balance and multiple stress-response pathways including those controlled by PKA. The impact of this compound on trehalose regulation, however, remains unclear. To determine how PKA activity influences trehalose regulation under boron stress, we analyzed NTH1 promoter activity and trehalose accumulation in a wild type and a PKA-hyperactive mutant in yeast cells across three physiological phases: early exponential growth, extended exposure, and the post-diauxic state. In the wild type, boric acid suppressed NTH1 promoter activity in the early phase but markedly increased trehalose levels, indicating enhanced synthesis during limited trehalase expression. The PKA-hyperactive mutant showed almost no induction of trehalose in this phase, revealing a loss of normal stress-responsive trehalose accumulation. During extended exposure, boric acid reduced trehalose only in wild type, suggesting impaired synthesis after prolonged stress; the mutant again showed minimal change. In the post-diauxic phase, boric acid triggered a regulatory shift in the wild type, with high trehalose and modest NTH1 activation, while the mutant remained unresponsive. Together, these results demonstrated that boric acid modifies trehalose regulation in a strongly PKA-dependent and phase-specific manner, and that elevated PKA activity restricts metabolic flexibility and prevents appropriate trehalose remodeling under boron stress.