Involvement of mitochondrial proteins in calcium signaling and cell death induced by staurosporine in Neurospora crassa

Staurosporine-induced cell death in Neurospora crassa includes a well defined sequence of alterations in cytosolic calcium levels, comprising extracellular Ca2 + influx and mobilization of Ca2 + from internal stores. Here, we show that cells undergoing respiratory stress due to the lack of certain components of the mitochondrial complex I (like the 51 kDa and 14 kDa subunits) or the Ca2 +-binding alternative NADPH dehydrogenase NDE-1 are hypersensitive to staurosporine and incapable of setting up a proper intracellular Ca2 + response. Cells expressing mutant forms of NUO51 that mimic human metabolic diseases also presented Ca2 + signaling deficiencies. Accumulation of reactive oxygen species is increased in cells lacking NDE-1 and seems to be required for Ca2 + oscillations in response to staurosporine. Measurement of the mitochondrial levels of Ca2 + further supported the involvement of these organelles in staurosporine-induced Ca2 + signaling. In summary, our data indicate that staurosporine-induced fungal cell death involves a sophisticated response linking Ca2 + dynamics and bioenergetics.