Artículo
Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
Autor/es | Serrano Bueno, Gloria
Hernández, Agustín López Lluch, Guillermo Pérez Castiñeira, José Román Navas, Plácido Serrano Delgado, Aurelio |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Fecha de publicación | 2013 |
Fecha de depósito | 2022-02-08 |
Publicado en |
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Resumen | 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 ... 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 G 1/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. |
Identificador del proyecto | P07-CVI-3082
BFU2007-61887 BFU2010-15622 FIS-PI080500 P08-CTS-3988 |
Cita | Serrano Bueno, G., Hernández, A., López Lluch, G., Pérez Castiñeira, J.R., Navas, P. y Serrano Delgado, A. (2013). Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast. Journal of Biological Chemistry, 288 (18), 13082-13092. |
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