Teja Manda, Delight Hwarari, Raphael Dzinyela
Cisplatin increased MCU expression and reduced SERCA2 expression; the cisplatin-induced increase in MCU was partially reversed by BAPTA-AM and the endoplasmic reticulum stress inhibitor 4-PBA. MCU knockdown did not affect basal cell viability but attenuated cisplatin-induced reductions in viability, TUNEL positivity, and cleaved caspase-3. It was also associated with increased SERCA2 and decreased IP3R, GRP75, and VDAC1 expression. RNA sequencing identified differentially expressed genes enriched in autophagy-related processes and mTOR signaling. MCU knockdown was associated with increased PI3K/AKT/mTOR signaling and changes in Beclin1, LC3B-II, and p62. Ru360 cotreatment partially reproduced the protective phenotype in vitro and was associated with attenuated ABR threshold elevation at selected frequencies and reduced outer hair cell loss in vivo.
Crosstalk among MAPKs, CDPKs, SnRKs, and TOR establishes a dynamic regulatory framework that balances energy homeostasis, defense, and development under stress conditions. Continued advances in systems biology and functional genomics will further clarify these complex interactions and accelerate the development of crops with enhanced stress resilience, growth stability, and resource-use efficiency. Plants rely on complex kinase signaling networks to sense, integrate, and respond to rapidly fluctuating environmental stresses. Central to these networks are mitogen-activated protein kinases (MAPKs), calcium-dependent protein kinases (CDPKs), sucrose non-fermenting-1-related kinases (SnRKs), and the Target of Rapamycin (TOR) complex, which collectively coordinate stress perception, metabolic regulation, and growth adaptation. Although the individual functions of these pathways have been extensively characterized, a unified mechanistic framework describing their interconnected roles across diverse stress conditions remains incomplete. Here, we synthesize recent advances in plant stress signaling to propose an integrated model of kinase crosstalk that highlights key nodes of convergence, reciprocal regulation, and metabolic-hormonal integration. We emphasize the antagonistic interplay between SnRK1 and TOR as a central regulatory hub controlling energy balance and stress adaptation, while MAPK and CDPK cascades intersect with SnRK1-mediated autophagy and TOR-dependent anabolic growth pathways. In addition, hormonal signaling networks involving abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA) provide further layers of regulatory coordination that improve cellular responses to environmental stress. Collectively, these interconnected kinase networks orchestrate survival strategies, metabolic homeostasis, and resilience under adverse conditions. By integrating these signaling modules into a systems-level framework, this review provides mechanistic insights and emerging perspectives for engineering crops with enhanced stress tolerance, growth stability, and energy-use efficiency.