Endonuclease G regulates budding yeast life and death.
Endonuclease G (EndoG) is located in mitochondria yet translocates into the nucleus of apoptotic cells during human degenerative diseases. Nonetheless, a direct involvement of EndoG in cell-death execution remains equivocal, and the mechanism for mitochondrio-nuclear translocation is not known. Here, we show that the yeast homolog of EndoG (Nuc1p) can efficiently trigger apoptotic cell death when excluded from mitochondria. Nuc1p induces apoptosis in yeast independently of metacaspase or of apoptosis inducing factor. Instead, the permeability transition pore, karyopherin Kap123p, and histone H2B interact with Nuc1p and are required for cell death upon Nuc1p overexpression, suggesting a pathway in which mitochondrial pore opening, nuclear import, and chromatin association are successively involved in EndoG-mediated death. Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual--lethal and vital--roles for EndoG.
Büttner
Sabrina
S
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Eisenberg
Tobias
T
Carmona-Gutierrez
Didac
D
Ruli
Doris
D
Knauer
Heide
H
Ruckenstuhl
Christoph
C
Sigrist
Carola
C
Wissing
Silke
S
Kollroser
Manfred
M
Fröhlich
Kai-Uwe
KU
Sigrist
Stephan
S
Madeo
Frank
F
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D006657:Histones / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D028961:beta Karyopherins
D002352:Carrier Proteins; D006657:Histones; C109173:Kap123 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D028961:beta Karyopherins; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C052391:endonuclease G; D020169:Caspases; C456272:MCA1 protein, S cerevisiae