The yeast model system as a tool towards the understanding of apoptosis regulation by sphingolipids

Abstract

It has been established that sphingolipids are engaged in the regulation of apoptosis both as direct executors and as signalling molecules. However, the peculiarities of this class of bioactive lipids, namely the interconnectivity of their metabolic pathways, the specific subcellular localization where they are generated and the transport mechanisms involved, introduce a considerably high level of complexity in deciphering their role in the signalling and regulation of programmed cell death. Although yeast is undeniably a simple model, the conservation of the sphingolipid metabolism and of the core machinery engaged in regulated cell death has already provided valuable clues to the understanding of metabolic pathways involved in distinct cellular processes, including apoptosis. It can be anticipated that studies using this model system will further unravel mechanisms underlying the regulation of apoptosis by sphingolipids and contribute to novel therapeutic strategies against serious human diseases associated with dysfunction of sphingolipid-dependent cell death programmes.

The plant decapeptide OSIP108 prevents copper-induced apoptosis in yeast and human cells

“…Sphingolipid generating pathways are well conserved between yeast and mammalian cells and both produce dhSph as the second intermediate in de novo sphingolipid biosynthesis [46]. We chose to validate the sphingolipidomics data in yeast by investigating the effect of exogenous addition of dhSph in our yeast model for Cu-induced cell death, in the presence or absence of OSIP108, as OSIP108 apparently downregulates all sphingoid bases and sphingolipids intermediates starting from dhSph.…”

Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells

“…Sphingolipids have been implicated in the regulation of cell senescence and apoptosis [18][19][20]. Importantly, disruption of sphingolipid flux and turnover has been associated with ageing and the onset of age-associated ailments such as neurodegenerative diseases, diabetes metabolic syndrome and cancer [35][36][37].…”

“…Mounting evidence from yeast to mammalian cells suggests that sphingolipids are involved in the regulation of mitochondrial function [17][18][19][20]. Ceramides are central molecules in the metabolism of sphingolipids.…”

“…Ceramides are central molecules in the metabolism of sphingolipids. In yeast, dihydroceramides and phytoceramides are synthesized by N-acylation of a long chain base (dihydrosphingosine or phytosphingosine, respectively) or generated by hydrolysis of complex sphingolipids (inositol phosphosphingolipids) mediated by Isc1p, an orthologue of mammalian neutral sphingomyelinase-2 [18][19][20]. Isc1p is essential for respiratory metabolism.…”

Sphingolipids and mitochondrial function in budding yeast

“…SL biosynthetic pathways are highly conserved between mammalian and yeast cells [6-8]. In Saccharomyces cerevisiae de novo SL biosynthesis (Fig.…”