Table 1.
Lipid- or lipid metabolism-related regimens affect cell death and survival in yeast. The table summarizes the most important genetic or pharmacological regimens associated with lipids and lipid metabolism that lead to cell death or cell protection in the yeast Saccharomyces cerevisiae. If monitored by referenced studies, alterations in lipid profiles are depicted. The cell death and stress markers that led to respective phenotype conclusions are also included
| Treatment/regimen | Lipid alterations | Phenotype | Death and Stress Markers/Pathway | References |
|---|---|---|---|---|
|
LCB1 LCB2 knockdown OR SPT inhibitor myriocin |
Reduction in LCBs, general sphingolipids | Growth impairment; increased CLS; heat shock and H2O2 resistance | OD; clonogenicity: drop tests | Huang et al. (2012) |
| IPC synthase inhibitor Aureobasidin A | Reduction in complex sphingolipids; increased ceramide |
Apoptosis and growth impairment | Clonogenicity, TUNEL, ROS/Yca1p and Ca2+ dependent | Cerantola et al. (2009) and Kajiwara et al. (2012) |
| Exogenous PHS to IPC synthase mutant cells | Ceramide-3 accumulation | Cell death or senescence | OD, clonogenicity | Nagiec et al. (1997) |
|
AUR1 overexpression; Heterologous expression of mSMS1 |
n.d. | H2O2, heat shock, and Bax resistance; resistance to C2-ceramide or PHS |
Clonogenicity, drop tests | Yang et al. (2006) |
| Exogenous C2-ceramide | n.d. | Apoptotic and necrotic cell death | TUNEL, AnnV/PI, clonogenicity/mitochondrion dependent | Carmona-Gutierrez et al. (2011) and Galluzzi et al. (2012) |
| YDC1 overexpression | n.d. | Reduced CLS preventable by exogenous C6-dihydroceramide; apoptotic death |
Clonogenicity; TUNEL, AnnV/PI, MF |
Aerts et al. (2008) |
| ISC1 or LAG1 deletion | General ceramide decreased, but increased α-hydroxy-C20-phytoceramide | Resistance to acetic acid-induced cell death/apoptosis | Clonogenicity, ROS, MF, cytochrome c release | Rego et al. (2012) |
| ISC1 deletion | Mitochondrial ceramide decreased, but increased C26-phytoceramide; ceramide increased during CLS |
Reduced CLS, sensitivity to H2O2, apoptotic cell death | Clonogenicity, ROS, TUNEL/Yca1p and PP2A(Sit4p) dependent | Kitagaki et al. (2007) and Almeida et al. (2008) and Barbosa (2011) |
|
LAG1 deletion; LAG1 overexpression |
n.d. | Increased RLS; bimodal effect on RLS |
RLS analysis | D'mello et al. (1994) and Jiang et al. (2004) |
| Edelfosine | Lipidomic alterations in PC metabolism; reduced sterols and sphingolipids in lipid rafts |
Cell death, Pma1p degradation-dependent acidification | Clonogenicity, drop tests | Zaremberg et al. (2005) and Czyz et al. (2013) |
| Edelfosine | n.d. | α-tocopherol inhibitable apoptotic cell death | Growth, ROS, TUNEL | Zhang et al. (2007) |
| GUP1 deletion | n.d. | Reduced CLS with enhanced necrotic death | Clonogenicity, ROS, AnnV/PI, DAPI staining | Tulha et al. (2012) |
| UFAs applied to TAG/SE devoid cells (quadruple mutant*) | Increased FFA and phospholipids | Apoptotic cell death and activation of UPR | Clonogenicity, AnnV/PI, ROS | Garbarino et al. (2009) |
| UFAs applied to TAG/SE devoid cells (quadruple mutant*) | Accumulation of membranes and unsaturated phospholipids | Necrotic cell death, Dga1p-/Lro1p-complementable growth impairment | Growth, clonogenicity, AnnV/PI, ROS/ mitochondrion dependent |
Petschnigg et al. (2009) and Rockenfeller et al. (2010) |
| PAH1 deletion | Reduced levels of TAG, DAG; increased PA and phospholipid levels |
Apoptotic cell death in stationary phase, FFA sensitivity |
Growth, AnnV/PI | Fakas et al. (2011) |
| SFA (Decanoic acid, valproic acid) | Accumulation of neutral lipids | Apoptotic cell death | Growth, clonogenicity, ROS, AnnV/PI, TUNEL/ Yca1p and Sir2p dependent |
Stratford & Anslow (1996), Mitsui et al. (2005) and Sun et al. (2007) |
| PEX5 deletion | Increased TAG, DAG and FFA levels | Reduced CLS | Clonogenicity | Goldberg et al. (2010) |
| PEX6 deletion | n.d. | Sensitivity to H2O2 and acetic acid; increased necrosis during aging; reduced CLS | Clonogenicity, ROS, AnnV/PI | Meijer et al. (2007) |
AnnV/PI, annexin V and propidium iodide costaining; CLS, chronological life span; IPC, inositol phosphorylceramide; mSMS1, murine sphingomyelin synthase; MF, mitochondrial fragmentation; OD, optical density; PA, phosphatidic acid; PC, phosphatidylcholine; PHS, phytosphingosine; PP2A, protein phosphatase 2A; RLS, replicative life span; ROS, reactive oxygen species; SFA, saturated fatty acid; SPT, serine palmitoyltransferase; TUNEL, TdT-mediated dUTP nick end labeling; UFA, unsaturated fatty acid
Please refer to text for explanation.