RT Journal Article T1 Cytosolic pH Controls Fungal MAPK Signaling and Pathogenicity A1 Martín Brieva, Humberto A1 Fernández-Acero Bascones, Teresa A1 Fernandes TR, A1 Mariscal M, A1 Serrano A, A1 Segorbe D, A1 Turrà D, A1 Di Pietro A, AB Mitogen-activated protein kinases (MAPKs) regulate a variety of cellular processes in eukaryotes. In fungal pathogens, conserved MAPK pathways control key virulence functions such as infection-related development, invasive hyphal growth, or cell wall remodeling. Recent findings suggest that ambient pH acts as a key regulator of MAPK-mediated pathogenicity, but the underlying molecular events are unknown. Here, we found that in the fungal pathogen Fusarium oxysporum, pH controls another infection-related process, hyphal chemotropism. Using the ratiometric pH sensor pHluorin we show that fluctuations in cytosolic pH (pHc) induce rapid reprogramming of the three conserved MAPKs in F. oxysporum, and that this response is conserved in the fungal model organism Saccharomyces cerevisiae. Screening of a subset of S. cerevisiae mutants identified the sphingolipid-regulated AGC kinase Ypk1/2 as a key upstream component of pHc-modulated MAPK responses. We further show that acidification of the cytosol in F. oxysporum leads to an increase of the long-chain base (LCB) sphingolipid dihydrosphingosine (dhSph) and that exogenous addition of dhSph activates Mpk1 phosphorylation and chemotropic growth. Our results reveal a pivotal role of pHc in the regulation of MAPK signaling and suggest new ways to target fungal growth and pathogenicity. PB Reinhard Fischer, Karlsruhe Institute of Technology (KIT) YR 2023 FD 2023-03-02 LK https://hdl.handle.net/20.500.14352/114961 UL https://hdl.handle.net/20.500.14352/114961 LA eng NO Fernandes TR, Mariscal M, Serrano A, Segorbe D, Fernández-Acero T, Martín H, et al. Cytosolic pH Controls Fungal MAPK Signaling and Pathogenicity. mBio 2023;14:e00285-23. https://doi.org/10.1128/mbio.00285-23. NO Ministerio de Ciencia e Innovación (España) NO Junta de Andalucía DS Docta Complutense RD 7 abr 2025