TY - JOUR
T1 - Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation
AU - Speer, Natalie Ortiz
AU - Jay Braun, R.
AU - Reynolds, Emma Grace
AU - Brudnicka, Alicja
AU - Swanson, Jessica M.J.
AU - Mike Henne, W.
N1 - Publisher Copyright:
© 2023 Speer et al.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Cells store lipids in the form of triglyceride (TG) and sterol ester (SE) in lipid droplets (LDs). Distinct pools of LDs exist, but a pervasive question is how proteins localize to and convey functions to LD subsets. Here, we show that the yeast protein YDR275W/Tld1 (for TG-associated LD protein 1) localizes to a subset of TG-containing LDs and reveal it negatively regulates lipolysis. Mechanistically, Tld1 LD targeting requires TG, and it is mediated by two distinct hydrophobic regions (HRs). Molecular dynamics simulations reveal that Tld1’s HRs interact with TG on LDs and adopt specific conformations on TG-rich LDs versus SE-rich LDs in yeast and human cells. Tld1-deficient yeast display no defect in LD biogenesis but exhibit elevated TG lipolysis dependent on lipase Tgl3. Remarkably, overexpression of Tld1, but not LD protein Pln1/Pet10, promotes TG accumulation without altering SE pools. Finally, we find that Tld1-deficient cells display altered LD mobilization during extended yeast starvation. We propose that Tld1 senses TG-rich LDs and regulates lipolysis on LD subpopulations.
AB - Cells store lipids in the form of triglyceride (TG) and sterol ester (SE) in lipid droplets (LDs). Distinct pools of LDs exist, but a pervasive question is how proteins localize to and convey functions to LD subsets. Here, we show that the yeast protein YDR275W/Tld1 (for TG-associated LD protein 1) localizes to a subset of TG-containing LDs and reveal it negatively regulates lipolysis. Mechanistically, Tld1 LD targeting requires TG, and it is mediated by two distinct hydrophobic regions (HRs). Molecular dynamics simulations reveal that Tld1’s HRs interact with TG on LDs and adopt specific conformations on TG-rich LDs versus SE-rich LDs in yeast and human cells. Tld1-deficient yeast display no defect in LD biogenesis but exhibit elevated TG lipolysis dependent on lipase Tgl3. Remarkably, overexpression of Tld1, but not LD protein Pln1/Pet10, promotes TG accumulation without altering SE pools. Finally, we find that Tld1-deficient cells display altered LD mobilization during extended yeast starvation. We propose that Tld1 senses TG-rich LDs and regulates lipolysis on LD subpopulations.
UR - http://www.scopus.com/inward/record.url?scp=85175271945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175271945&partnerID=8YFLogxK
U2 - 10.1083/jcb.202303026
DO - 10.1083/jcb.202303026
M3 - Article
C2 - 37889293
AN - SCOPUS:85175271945
SN - 0021-9525
VL - 223
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
M1 - e202303026
ER -