2024-03-28T14:07:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1292042021-11-22T13:09:14Zcom_10261_80com_10261_1com_10261_128col_10261_333col_10261_381
Serrano-Bueno, Gloria
Hernández, Agustín
López-Lluch, Guillermo
Pérez-Castiñeira, J. R.
Navas, Plácido
Serrano, Aurelio
2016-02-18T11:20:41Z
2016-02-18T11:20:41Z
2013
Journal of Biological Chemistry 288(18): 13082-13092 (2013)
0021-9258
http://hdl.handle.net/10261/129204
10.1074/jbc.M112.439349
1083-351X
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003751
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100011011
23479727
Inorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase, we show that respiring cells arrest in S phase upon Ipp1p deficiency, but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G1/G0 phase and suffer massive vacuolization and eventual cell death by autophagy. Impaired NAD(+) metabolism is a major determinant of cell death in this scenario because demise can be avoided under conditions favoring accumulation of the oxidized pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the energy metabolism of the cell.
eng
closedAccess
Autophagy
Cell death
Energy metabolism
NAD
Yeast metabolism
Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
artículo