title: Involvement of mitochondrial proteins in calcium signaling and cell death induced by staurosporine in Neurospora crassa.
abstract: Staurosporine-induced cell death in Neurospora crassa includes a well defined sequence of alterations in cytosolic calcium levels, comprising extracellular Ca(2+) influx and mobilization of Ca(2+) 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 51kDa and 14kDa subunits) or the Ca(2+)-binding alternative NADPH dehydrogenase NDE-1 are hypersensitive to staurosporine and incapable of setting up a proper intracellular Ca(2+) response. Cells expressing mutant forms of NUO51 that mimic human metabolic diseases also presented Ca(2+) signaling deficiencies. Accumulation of reactive oxygen species is increased in cells lacking NDE-1 and seems to be required for Ca(2+) oscillations in response to staurosporine. Measurement of the mitochondrial levels of Ca(2+) further supported the involvement of these organelles in staurosporine-induced Ca(2+) signaling. In summary, our data indicate that staurosporine-induced fungal cell death involves a sophisticated response linking Ca(2+) dynamics and bioenergetics.
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: apgoncalves@berkeley.edu.
authors.forename: A Pedro
authors.initials: AP
authors.lastname: Gonçalves
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: J Miguel
authors.initials: JM
authors.lastname: Cordeiro
authors.affiliation: IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Monteiro
authors.affiliation: IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lucchi
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Correia-de-Sá
authors.affiliation: ICBAS-Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: avideira@ibmc.up.pt.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
keywords: Alternative NAD(P)H dehydrogenase; Ca(2+) dynamics; Cell death; Complex I; Mitochondrion; NDE-1