Inhibition of respiration prompts commitment to unisexual reproduction in Cryptococcus deneoformans 

Cell Rep. 2025 Nov 22;44(12):116603. doi: 10.1016/j.celrep.2025.116603. Online ahead of print.

ABSTRACT

In the human fungal pathogen Cryptococcus deneoformans, sexual reproduction facilitates evolution and adaptation. This fungus can undergo two sexual modes: α × a sexual reproduction and unisexual reproduction (without mating partner cooperation), with α-unisexual reproduction predominating. However, the mechanism driving commitment to α-unisexual reproduction has remained elusive. Here, through a multilayered genetic screen of transfer DNA (T-DNA) insertional mutants, we identified several mutants with enhanced unisexual reproduction but impaired α × a heterothallic mating. Genome sequencing of these mutants revealed that the T-DNA insertions are enriched in genes involved in respiration. Consistently, pharmacological inhibition of respiration recapitulated this phenotype. This respiratory-inhibition-prompted selection for unisexual development requires the filamentation activator Znf2, which directly inhibits the cyclin Cln1, resulting in cell-cycle arrest in the G2/M phase, which promotes unisexual development but functionally excludes α × a heterothallic mating. Collectively, our findings uncover a mechanism that commits unisexual reproduction through respiratory inhibition.

PMID:41275490 | DOI:10.1016/j.celrep.2025.116603