A starvation-specific serine protease gene, isp6+, is involved in both autophagy and sexual development in...

Schizosaccharomyces pombe isp6(+) gene encodes a vacuolar serine protease, which is specifically induced during nitrogen starvation. An isp6-disruption mutant, isp6Delta, grew normally under normal conditions but was defective in large-scale protein degradation during nitrogen starvation, a hallmark of autophagy. Vacuoles are the organelles for such drastic protein degradation but those of isp6Delta were apparently aberrant. isp6Delta was infertile under nitrogen source-free conditions with poor expression of ste11(+), a gene critical for sexual development. A protein kinase A-disruption mutant, pka1Delta, is prone to sexual development because expression of ste11(+) is derepressed. However, isp6Deltapka1Delta still showed defects in ste11(+) expression and sexual development under nitrogen source-free conditions. isp6Delta and isp6Deltapka1Delta were able to initiate sexual development to produce spores when only a small amount of a nitrogen source was present. Pat1 protein kinase negatively controls meiosis, and a temperature-sensitive mutant of pat1, pat1-114, initiates meiosis irrespective of ploidy at the restrictive temperature. However, isp6Deltapat1-114 did not start meiosis under nitrogen source-free conditions even at the restrictive temperature. These observations suggest that isp6(+) contributes to sexual development by providing a nitrogen source through autophagy.