Activation of the Hog1p kinase in Isc1p-deficient yeast cells is associated with mitochondrial dysfunction, oxidative stress sensitivity and premature aging

• Type: Article in International Scientific Journal
• Date: 2012

Authors

António Barbosa (Author) ICBAS; João Graça (Author) ICBAS; Vanda Mendes (Author) ICBAS; Susana R. Chaves (Author) Other; Maria Amélia Amorim (Author) ICBAS; Marta Vaz Mendes (Author) Other; Pedro Gaspar Ferreira (Author) ICBAS; Vitor Costa (Author) Other

Journal

Title: Mechanisms of Ageing and Development

Vol. 133 No. 5

Pages: 317-330

ISSN: 0047-6374

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 24 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-ABM

DOI: 10.1016/j.mad.2012.03.007

Abstract (EN): The Saccharomyces cerevisiae Isc1p, an orthologue of mammalian neutral sphingomyelinase 2, plays a key role in mitochondrial function, oxidative stress resistance and chronological lifespan. Isc1p functions upstream of the ceramide-activated protein phosphatase Sit4p through the modulation of ceramide levels. Here, we show that both ceramide and loss of Isc1p lead to the activation of Hog1p, the MAPK of the high osmolarity glycerol (HOG) pathway that is functionally related to mammalian p38 and JNK. The hydrogen peroxide sensitivity and premature aging of isc1 Delta cells was partially suppressed by HOG1 deletion. Notably. Hog1p activation mediated the mitochondrial dysfunction and catalase A deficiency associated with oxidative stress sensitivity and premature aging of isc1 Delta cells. Downstream of Hog1p, Isc1p deficiency activated the cell wall integrity (CWI) pathway. Deletion of the SLT2 gene, which encodes for the MAPK of the CWI pathway, was lethal in isc1 Delta cells and this mutant strain was hypersensitive to cell wall stress. However, the phenotypes of isc1 Delta cells were not associated with cell wall defects. Our findings support a role for Hogp in the regulation of mitochondrial function and suggest that constitutive activation of Hog1p is deleterious for isc1 Delta cells under oxidative stress conditions and during chronological aging.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14