Cdk1/Cdc28-dependent activation of the major triacylglycerol lipase Tgl4 in yeast links lipolysis to cell-cycle progression.
Triacylglycerols (TGs) serve essential cellular functions as reservoirs for energy substrates (fatty acids) and membrane lipid precursors (diacylglycerols and fatty acids). Here we show that the major yeast TG lipase Tgl4, the functional ortholog of murine adipose TG lipase ATGL, is phosphorylated and activated by cyclin-dependent kinase 1 (Cdk1/Cdc28). Phospho-Tgl4-catalyzed lipolysis contributes to early bud formation in late G1 phase of the cell cycle. Conversely, lack of lipolysis delays bud formation and cell-cycle progression. In the absence of beta-oxidation, lipolysis-derived metabolites are thus required to support cellular growth. TG homeostasis is the only metabolic process identified as yet that is directly regulated by Cdk1/Cdc28-dependent phosphorylation of key anabolic and catabolic enzymes, highlighting the importance of FA storage and mobilization during the cell cycle. Our data provide evidence for a direct link between cell-cycle-regulatory kinases and TG degradation and suggest a general mechanism for coordinating membrane synthesis with cell-cycle progression.
Kurat
Christoph F
CF
Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, A8010 Graz, Austria.
Wolinski
Heimo
H
Petschnigg
Julia
J
Kaluarachchi
Supipi
S
Andrews
Brenda
B
Natter
Klaus
K
Kohlwein
Sepp D
SD
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism*; D002453:Cell Cycle; D004789:Enzyme Activation; D005227:Fatty Acids / Q000096:biosynthesis; D016193:G1 Phase; D006706:Homeostasis; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D008055:Lipids; D008066:Lipolysis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D008055:Lipids; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; D010769:Phosphothreonine; D010768:Phosphoserine; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D008049:Lipase; C506904:Tgl4 protein, S cerevisiae