Lipid droplets and cellular lipid flux.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
30
07
2023
accepted:
24
01
2024
medline:
18
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
ppublish
Résumé
Lipid droplets are dynamic organelles that store neutral lipids, serve the metabolic needs of cells, and sequester lipids to prevent lipotoxicity and membrane damage. Here we review the current understanding of the mechanisms of lipid droplet biogenesis and turnover, the transfer of lipids and metabolites at membrane contact sites, and the role of lipid droplets in regulating fatty acid flux in lipotoxicity and cell death.
Identifiants
pubmed: 38454048
doi: 10.1038/s41556-024-01364-4
pii: 10.1038/s41556-024-01364-4
doi:
Substances chimiques
Fatty Acids
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
331-345Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01GM112948
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01DK128099
Informations de copyright
© 2024. Springer Nature Limited.
Références
Olzmann, J. A. & Carvalho, P. Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol. 20, 137–155 (2019).
pubmed: 30523332
pmcid: 6746329
doi: 10.1038/s41580-018-0085-z
Farese, R. V. & Walther, T. C. Glycerolipid synthesis and lipid droplet formation in the endoplasmic reticulum. Cold Spring Harb. Perspect. Biol. 15, a041246 (2023).
pubmed: 36096640
doi: 10.1101/cshperspect.a041246
Zadoorian, A., Du, X. & Yang, H. Lipid droplet biogenesis and functions in health and disease. Nat. Rev. Endocrinol. 19, 443–459 (2023).
pubmed: 37221402
doi: 10.1038/s41574-023-00845-0
Petan, T. Lipid droplets in cancer. Rev. Physiol. Biochem Pharm. 185, 53–86 (2023).
Ralhan, I., Chang, C.-L., Lippincott-Schwartz, J. & Ioannou, M. S. Lipid droplets in the nervous system. J. Cell Biol. 220, e202102136 (2021).
pubmed: 34152362
pmcid: 8222944
doi: 10.1083/jcb.202102136
Bosch, M., Sweet, M. J., Parton, R. G. & Pol, A. Lipid droplets and the host–pathogen dynamic: FATal attraction? J. Cell Biol. 220, e202104005 (2021).
pubmed: 34165498
pmcid: 8240858
doi: 10.1083/jcb.202104005
Papsdorf, K. et al. Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids. Nat. Cell Biol. 25, 672–684 (2023).
pubmed: 37127715
pmcid: 10185472
doi: 10.1038/s41556-023-01136-6
Kumar, A. V. et al. Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans. iScience 26, 107960 (2023).
pubmed: 37810233
pmcid: 10551902
doi: 10.1016/j.isci.2023.107960
Roberts, M. A. & Olzmann, J. A. Protein quality control and lipid droplet metabolism. Annu. Rev. Cell Dev. Biol. 36, 115–139 (2020).
pubmed: 33021827
pmcid: 7593838
doi: 10.1146/annurev-cellbio-031320-101827
Dumesnil, C. et al. Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols. Nat. Commun. 14, 915 (2023).
pubmed: 36807572
pmcid: 9938224
doi: 10.1038/s41467-023-36375-6
Mahamid, J. et al. Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association. Proc. Natl Acad. Sci. USA 116, 16866–16871 (2019).
pubmed: 31375636
pmcid: 6708344
doi: 10.1073/pnas.1903642116
Rogers, S. et al. Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome. J. Cell Biol. 221, e202205053 (2022).
pubmed: 36112368
pmcid: 9485706
doi: 10.1083/jcb.202205053
Henne, W. M. The (social) lives, deaths, and biophysical phases of lipid droplets. Curr. Opin. Cell Biol. 82, 102178 (2023).
pubmed: 37295067
pmcid: 10782554
doi: 10.1016/j.ceb.2023.102178
Sui, X. et al. Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme. Nature 581, 323–328 (2020).
pubmed: 32433611
pmcid: 7398557
doi: 10.1038/s41586-020-2289-6
Wang, L. et al. Structure and mechanism of human diacylglycerol O-acyltransferase 1. Nature 581, 329–332 (2020).
pubmed: 32433610
pmcid: 7255049
doi: 10.1038/s41586-020-2280-2
McLelland, G.-L. et al. Identification of an alternative triglyceride biosynthesis pathway. Nature 621, 171–178 (2023).
pubmed: 37648867
pmcid: 10482677
doi: 10.1038/s41586-023-06497-4
Thiam, A. R. & Ikonen, E. Lipid droplet nucleation. Trends Cell Biol. 31, 108–118 (2021).
pubmed: 33293168
doi: 10.1016/j.tcb.2020.11.006
Walther, T. C., Kim, S., Arlt, H., Voth, G. A. & Farese, R. V. Structure and function of lipid droplet assembly complexes. Curr. Opin. Struct. Biol. 80, 102606 (2023).
pubmed: 37150040
pmcid: 10853036
doi: 10.1016/j.sbi.2023.102606
Wang, H. et al. Seipin is required for converting nascent to mature lipid droplets. eLife 5, e16582 (2016).
pubmed: 27564575
pmcid: 5035145
doi: 10.7554/eLife.16582
Salo, V. T. et al. Seipin facilitates triglyceride flow to lipid droplet and counteracts droplet ripening via endoplasmic reticulum contact. Dev. Cell 50, 478–493.e9 (2019).
pubmed: 31178403
doi: 10.1016/j.devcel.2019.05.016
Sui, X. et al. Cryo-electron microscopy structure of the lipid droplet-formation protein seipin. J. Cell Biol. 217, 4080–4091 (2018).
pubmed: 30327422
pmcid: 6279392
doi: 10.1083/jcb.201809067
Yan, R. et al. Human SEIPIN binds anionic phospholipids. Dev. Cell 47, 248–256.e4 (2018).
pubmed: 30293840
doi: 10.1016/j.devcel.2018.09.010
Arlt, H. et al. Seipin forms a flexible cage at lipid droplet formation sites. Nat. Struct. Mol. Biol. 29, 194–202 (2022).
pubmed: 35210614
pmcid: 8930772
doi: 10.1038/s41594-021-00718-y
Klug, Y. A. et al. Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex. Nat. Commun. 12, 5892 (2021).
pubmed: 34625558
pmcid: 8501077
doi: 10.1038/s41467-021-26162-6
Kim, S. et al. Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane. eLife 11, e75808 (2022).
pubmed: 35583926
pmcid: 9122495
doi: 10.7554/eLife.75808
Zoni, V. et al. Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure. Proc. Natl Acad. Sci. USA 118, e2017205118 (2021).
pubmed: 33674387
pmcid: 7958289
doi: 10.1073/pnas.2017205118
Prasanna, X. et al. Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane. PLoS Biol. 19, e3000998 (2021).
pubmed: 33481779
pmcid: 7857593
doi: 10.1371/journal.pbio.3000998
Chorlay, A. et al. Membrane asymmetry imposes directionality on lipid droplet emergence from the ER. Dev. Cell 50, 25–42.e7 (2019).
pubmed: 31155466
doi: 10.1016/j.devcel.2019.05.003
Ben M’barek, K. et al. ER membrane phospholipids and surface tension control cellular lipid droplet formation. Dev. Cell 41, 591–604.e7 (2017).
pubmed: 28579322
doi: 10.1016/j.devcel.2017.05.012
Jiang, X. et al. Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis. J. Hepatol. 77, 619–631 (2022).
pubmed: 35452693
pmcid: 9449865
doi: 10.1016/j.jhep.2022.04.010
Li, Y. E. et al. TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine. J. Cell Biol. 220, e202103105 (2021).
pubmed: 33929485
pmcid: 8077175
doi: 10.1083/jcb.202103105
Morishita, H. et al. A critical role of VMP1 in lipoprotein secretion. eLife 8, e48834 (2019).
pubmed: 31526472
pmcid: 6748824
doi: 10.7554/eLife.48834
Huang, D. et al. TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis. Cell Metab. 33, 1655–1670.e8 (2021).
pubmed: 34015269
doi: 10.1016/j.cmet.2021.05.006
Mailler, E. et al. The autophagy protein ATG9A enables lipid mobilization from lipid droplets. Nat. Commun. 12, 6750 (2021).
pubmed: 34799570
pmcid: 8605025
doi: 10.1038/s41467-021-26999-x
Chung, J. et al. LDAF1 and seipin form a lipid droplet assembly complex. Dev. Cell 51, 551–563.e7 (2019).
pubmed: 31708432
pmcid: 7235935
doi: 10.1016/j.devcel.2019.10.006
Castro, I. G. et al. Promethin is a conserved seipin partner protein. Cells 8, 268 (2019).
pubmed: 30901948
pmcid: 6468817
doi: 10.3390/cells8030268
Joshi, A. S. et al. Lipid droplet and peroxisome biogenesis occur at the same ER subdomains. Nat. Commun. 9, 2940 (2018).
pubmed: 30054481
pmcid: 6063926
doi: 10.1038/s41467-018-05277-3
Joshi, A. S., Ragusa, J. V., Prinz, W. A. & Cohen, S. Multiple C2 domain–containing transmembrane proteins promote lipid droplet biogenesis and growth at specialized endoplasmic reticulum subdomains. Mol. Biol. Cell 32, 1147–1157 (2021).
pubmed: 33826368
pmcid: 8351558
doi: 10.1091/mbc.E20-09-0590
Ferreira, J. V. & Carvalho, P. Pex30-like proteins function as adaptors at distinct ER membrane contact sites. J. Cell Biol. 220, e202103176 (2021).
pubmed: 34402813
pmcid: 8374871
doi: 10.1083/jcb.202103176
Santinho, A. et al. Membrane curvature catalyzes lipid droplet assembly. Curr. Biol. 30, 2481–2494.e6 (2020).
pubmed: 32442467
doi: 10.1016/j.cub.2020.04.066
Renne, M. F., Corey, R. A., Ferreira, J. V., Stansfeld, P. J. & Carvalho, P. Seipin concentrates distinct neutral lipids via interactions with their acyl chain carboxyl esters. J. Cell Biol. 221, e202112068 (2022).
Molenaar, M. R. et al. Retinyl esters form lipid droplets independently of triacylglycerol and seipin. J. Cell Biol. 220, e202011071 (2021).
pubmed: 34323918
pmcid: 8327380
doi: 10.1083/jcb.202011071
Sołtysik, K. et al. Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner. J. Cell Biol. 220, e202005026 (2021).
pubmed: 33315072
doi: 10.1083/jcb.202005026
Olarte, M.-J., Swanson, J. M. J., Walther, T. C. & Farese, R. V. The CYTOLD and ERTOLD pathways for lipid droplet–protein targeting. Trends Biochem. Sci. 47, 39–51 (2022).
pubmed: 34583871
doi: 10.1016/j.tibs.2021.08.007
Wilfling, F. et al. Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev. Cell 24, 384–399 (2013).
pubmed: 23415954
pmcid: 3727400
doi: 10.1016/j.devcel.2013.01.013
Song, J. et al. Identification of two pathways mediating protein targeting from ER to lipid droplets. Nat. Cell Biol. 24, 1364–1377 (2022).
pubmed: 36050470
pmcid: 9481466
doi: 10.1038/s41556-022-00974-0
Schrul, B. & Kopito, R. R. Peroxin-dependent targeting of a lipid-droplet-destined membrane protein to ER subdomains. Nat. Cell Biol. 18, 740–751 (2016).
pubmed: 27295553
pmcid: 4925261
doi: 10.1038/ncb3373
Olzmann, J. A., Richter, C. M. & Kopito, R. R. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc. Natl Acad. Sci. USA 110, 1345–1350 (2013).
pubmed: 23297223
pmcid: 3557085
doi: 10.1073/pnas.1213738110
Olarte, M.-J. et al. Determinants of endoplasmic reticulum-to-lipid droplet protein targeting. Dev. Cell 54, 471–487.e7 (2020).
pubmed: 32730754
pmcid: 7696655
doi: 10.1016/j.devcel.2020.07.001
Boeszoermenyi, A. et al. Structure of a CGI-58 motif provides the molecular basis of lipid droplet anchoring. J. Biol. Chem. 290, 26361–26372 (2015).
pubmed: 26350461
pmcid: 4646293
doi: 10.1074/jbc.M115.682203
Grabner, G. F., Xie, H., Schweiger, M. & Zechner, R. Lipolysis: cellular mechanisms for lipid mobilization from fat stores. Nat. Metab. 3, 1445–1465 (2021).
pubmed: 34799702
doi: 10.1038/s42255-021-00493-6
Schott, M. B., Rozeveld, C. N., Weller, S. G. & McNiven, M. A. Lipophagy at a glance. J. Cell Sci. 135, jcs259402 (2022).
pubmed: 35260889
pmcid: 9014375
doi: 10.1242/jcs.259402
Soni, K. G. et al. Coatomer-dependent protein delivery to lipid droplets. J. Cell Sci. 122, 1834–1841 (2009).
pubmed: 19461073
pmcid: 2684835
doi: 10.1242/jcs.045849
Wilfling, F. et al. Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting. eLife 3, e01607 (2014).
pubmed: 24497546
pmcid: 3913038
doi: 10.7554/eLife.01607
Beller, M. et al. COPI complex is a regulator of lipid homeostasis. PLoS Biol. 6, e292 (2008).
pubmed: 19067489
pmcid: 2586367
doi: 10.1371/journal.pbio.0060292
Zechner, R., Madeo, F. & Kratky, D. Cytosolic lipolysis and lipophagy: two sides of the same coin. Nat. Rev. Mol. Cell Biol. 18, 671–684 (2017).
pubmed: 28852221
doi: 10.1038/nrm.2017.76
Lass, A. et al. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 3, 309–319 (2006).
pubmed: 16679289
doi: 10.1016/j.cmet.2006.03.005
Kimmel, A. R. & Sztalryd, C. The perilipins: major cytosolic lipid droplet-associated proteins and their roles in cellular lipid storage, mobilization, and systemic homeostasis. Annu. Rev. Nutr. 36, 471–509 (2016).
pubmed: 27431369
doi: 10.1146/annurev-nutr-071813-105410
Granneman, J. G., Moore, H.-P. H., Mottillo, E. P., Zhu, Z. & Zhou, L. Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase. J. Biol. Chem. 286, 5126–5135 (2011).
pubmed: 21148142
doi: 10.1074/jbc.M110.180711
Yang, A., Mottillo, E. P., Mladenovic-Lucas, L., Zhou, L. & Granneman, J. G. Dynamic interactions of ABHD5 with PNPLA3 regulate triacylglycerol metabolism in brown adipocytes. Nat. Metab. 1, 560–569 (2019).
pubmed: 31497752
pmcid: 6730670
doi: 10.1038/s42255-019-0066-3
Wang, Y., Kory, N., BasuRay, S., Cohen, J. C. & Hobbs, H. H. PNPLA3, CGI-58, and inhibition of hepatic triglyceride hydrolysis in mice. Hepatology 69, 2427–2441 (2019).
pubmed: 30802989
doi: 10.1002/hep.30583
Sanders, M. A. et al. Endogenous and synthetic ABHD5 ligands regulate ABHD5-perilipin interactions and lipolysis in fat and muscle. Cell Metab. 22, 851–860 (2015).
pubmed: 26411340
pmcid: 4862007
doi: 10.1016/j.cmet.2015.08.023
Yang, X. et al. The G
pubmed: 20197052
pmcid: 3658843
doi: 10.1016/j.cmet.2010.02.003
DiStefano, M. T. et al. The lipid droplet protein hypoxia-inducible gene 2 promotes hepatic triglyceride deposition by inhibiting lipolysis. J. Biol. Chem. 290, 15175–15184 (2015).
pubmed: 25922078
pmcid: 4463459
doi: 10.1074/jbc.M115.650184
Tseng, Y. Y. et al. Structural and functional insights into ABHD5, a ligand-regulated lipase co-activator. Sci. Rep. 12, 2565 (2022).
pubmed: 35173175
pmcid: 8850477
doi: 10.1038/s41598-021-04179-7
Kulminskaya, N. et al. Unmasking crucial residues in adipose triglyceride lipase for coactivation with comparative gene identification-58. J. Lipid. Res. 65, 100491 (2024).
Kohlmayr, J. M. et al. Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis. Preprint at bioRxiv https://doi.org/10.1101/2023.05.10.540188 (2023)
Mayer, N. et al. Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat. Chem. Biol. 9, 785–787 (2013).
pubmed: 24096302
doi: 10.1038/nchembio.1359
Schott, M. B. et al. Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes. J. Cell Biol. 218, 3320–3335 (2019).
pubmed: 31391210
pmcid: 6781454
doi: 10.1083/jcb.201803153
Chung, J. et al. The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets. Nat. Cell Biol. 25, 1101–1110 (2023).
pubmed: 37443287
pmcid: 10415183
doi: 10.1038/s41556-023-01178-w
Herker, E., Vieyres, G., Beller, M., Krahmer, N. & Bohnert, M. Lipid droplet contact sites in health and disease. Trends Cell Biol. 31, 345–358 (2021).
pubmed: 33546922
doi: 10.1016/j.tcb.2021.01.004
Prinz, W. A., Toulmay, A. & Balla, T. The functional universe of membrane contact sites. Nat. Rev. Mol. Cell Biol. 21, 7–24 (2020).
pubmed: 31732717
doi: 10.1038/s41580-019-0180-9
Wong, L. H., Gatta, A. T. & Levine, T. P. Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes. Nat. Rev. Mol. Cell Biol. 20, 85–101 (2019).
pubmed: 30337668
doi: 10.1038/s41580-018-0071-5
Hanna, M., Guillén-Samander, A. & De Camilli, P. RBG motif bridge-like lipid transport proteins: structure, functions, and open questions. Annu. Rev. Cell Dev. Biol. 39, 409–434 (2023).
pubmed: 37406299
doi: 10.1146/annurev-cellbio-120420-014634
Du, X. et al. ORP5 localizes to ER-lipid droplet contacts and regulates the level of PI(4)P on lipid droplets. J. Cell Biol. 219, e201905162 (2020).
pubmed: 31653673
doi: 10.1083/jcb.201905162
Guyard, V. et al. ORP5 and ORP8 orchestrate lipid droplet biogenesis and maintenance at ER–mitochondria contact sites. J. Cell Biol. 221, e202112107 (2022).
pubmed: 35969857
pmcid: 9375143
doi: 10.1083/jcb.202112107
Olkkonen, V. M., Koponen, A. & Arora, A. OSBP-related protein 2 (ORP2): unraveling its functions in cellular lipid/carbohydrate metabolism, signaling and F-actin regulation. J. Steroid Biochem. Mol. Biol. 192, 105298 (2019).
pubmed: 30716465
doi: 10.1016/j.jsbmb.2019.01.016
Wang, T. et al. OSBPL2 is required for the binding of COPB1 to ATGL and the regulation of lipid droplet lipolysis. iScience 23, 101252 (2020).
pubmed: 32650117
pmcid: 7348002
doi: 10.1016/j.isci.2020.101252
Velikkakath, A. K. G., Nishimura, T., Oita, E., Ishihara, N. & Mizushima, N. Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol. Biol. Cell 23, 896–909 (2012).
pubmed: 22219374
pmcid: 3290647
doi: 10.1091/mbc.e11-09-0785
Korfhage, J. L. et al. ATG2A-mediated bridge-like lipid transport regulates lipid droplet accumulation. Preprint at bioRxiv https://doi.org/10.1101/2023.08.14.553257 (2023)
Bersuker, K. et al. A proximity labeling strategy provides insights into the composition and dynamics of lipid droplet proteomes. Dev. Cell 44, 97–112.e7 (2018).
pubmed: 29275994
doi: 10.1016/j.devcel.2017.11.020
Yeshaw, W. M. et al. Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility. eLife 8, e43561 (2019).
pubmed: 30741634
pmcid: 6389287
doi: 10.7554/eLife.43561
Kumar, N. et al. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. J. Cell Biol. 217, 3625–3639 (2018).
pubmed: 30093493
pmcid: 6168267
doi: 10.1083/jcb.201807019
Chen, S. et al. VPS13A and VPS13C influence lipid droplet abundance. Contact 5, 25152564221125613 (2022).
pubmed: 36147729
pmcid: 9491623
doi: 10.1177/25152564221125613
Ghanbarpour, A., Valverde, D. P., Melia, T. J. & Reinisch, K. M. A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis. Proc. Natl Acad. Sci. USA 118, e2101562118 (2021).
pubmed: 33850023
pmcid: 8072408
doi: 10.1073/pnas.2101562118
Van Vliet, A. R. et al. ATG9A and ATG2A form a heteromeric complex essential for autophagosome formation. Mol. Cell 82, 4324–4339.e8 (2022).
pubmed: 36347259
doi: 10.1016/j.molcel.2022.10.017
Matoba, K. et al. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. Nat. Struct. Mol. Biol. 27, 1185–1193 (2020).
pubmed: 33106658
doi: 10.1038/s41594-020-00518-w
Wang, H. et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J. Lipid Res. 52, 2159–2168 (2011).
pubmed: 21885430
pmcid: 3220284
doi: 10.1194/jlr.M017939
Miner, G. E. et al. PLIN5 interacts with FATP4 at membrane contact sites to promote lipid droplet-to-mitochondria fatty acid transport. Dev. Cell 58, 1250–1265.e6 (2023).
pubmed: 37290445
doi: 10.1016/j.devcel.2023.05.006
Hariri, H. et al. Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis. J. Cell Biol. 218, 1319–1334 (2019).
pubmed: 30808705
pmcid: 6446837
doi: 10.1083/jcb.201808119
Jägerström, S. et al. Lipid droplets interact with mitochondria using SNAP23. Cell Biol. Int. 33, 934–940 (2009).
pubmed: 19524684
doi: 10.1016/j.cellbi.2009.06.011
Ouyang, Q. et al. Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle. Dev. Cell 58, 289–305.e6 (2023).
pubmed: 36800997
doi: 10.1016/j.devcel.2023.01.007
Najt, C. P. et al. Lipid droplet-derived monounsaturated fatty acids traffic via PLIN5 to allosterically activate SIRT1. Mol. Cell 77, 810–824.e8 (2020).
pubmed: 31901447
doi: 10.1016/j.molcel.2019.12.003
Wang, J. et al. An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions. Nat. Commun. 12, 1252 (2021).
pubmed: 33623047
pmcid: 7902631
doi: 10.1038/s41467-021-21525-5
Nguyen, T. B. et al. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev. Cell 42, 9–21.e5 (2017).
pubmed: 28697336
pmcid: 5553613
doi: 10.1016/j.devcel.2017.06.003
Rambold, A. S., Cohen, S. & Lippincott-Schwartz, J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32, 678–692 (2015).
pubmed: 25752962
pmcid: 4375018
doi: 10.1016/j.devcel.2015.01.029
Benador, I. Y. et al. Mitochondria bound to lipid droplets have unique bioenergetics, composition, and dynamics that support lipid droplet expansion. Cell Metab. 27, 869–885.e6 (2018).
pubmed: 29617645
pmcid: 5969538
doi: 10.1016/j.cmet.2018.03.003
Freyre, C. A. C., Rauher, P. C., Ejsing, C. S. & Klemm, R. W. MIGA2 links mitochondria, the ER, and lipid droplets and promotes de novo lipogenesis in adipocytes. Mol. Cell 76, 811–825.e14 (2019).
pubmed: 31628041
doi: 10.1016/j.molcel.2019.09.011
Najt, C. P. et al. Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism. Cell Rep. 42, 112435 (2023).
pubmed: 37104088
pmcid: 10278152
doi: 10.1016/j.celrep.2023.112435
Gallardo-Montejano, V. I. et al. Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance. Nat. Commun. 12, 3320 (2021).
pubmed: 34083525
pmcid: 8175597
doi: 10.1038/s41467-021-23601-2
Gallardo-Montejano, V. I. et al. Nuclear perilipin 5 integrates lipid droplet lipolysis with PGC-1α/SIRT1-dependent transcriptional regulation of mitochondrial function. Nat. Commun. 7, 12723 (2016).
pubmed: 27554864
pmcid: 4999519
doi: 10.1038/ncomms12723
Hong, Z. et al. Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation. J. Cell Biol. 221, e202207022 (2022).
pubmed: 36282247
pmcid: 9597353
doi: 10.1083/jcb.202207022
Kim, H., Lee, S., Jun, Y. & Lee, C. Structural basis for mitoguardin-2 mediated lipid transport at ER-mitochondrial membrane contact sites. Nat. Commun. 13, 3702 (2022).
pubmed: 35764626
pmcid: 9239997
doi: 10.1038/s41467-022-31462-6
Listenberger, L. L., Ory, D. S. & Schaffer, J. E. Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J. Biol. Chem. 276, 14890–14895 (2001).
pubmed: 11278654
doi: 10.1074/jbc.M010286200
Zhu, X. G. et al. CHP1 regulates compartmentalized glycerolipid synthesis by activating GPAT4. Mol. Cell 74, 45–58.e7 (2019).
pubmed: 30846317
pmcid: 6450717
doi: 10.1016/j.molcel.2019.01.037
Piccolis, M. et al. Probing the global cellular responses to lipotoxicity caused by saturated fatty acids. Mol. Cell 74, 32–44.e8 (2019).
pubmed: 30846318
pmcid: 7696670
doi: 10.1016/j.molcel.2019.01.036
Masuda, M. et al. Saturated phosphatidic acids mediate saturated fatty acid–induced vascular calcification and lipotoxicity. J. Clin. Invest. 125, 4544–4558 (2015).
pubmed: 26517697
pmcid: 4665795
doi: 10.1172/JCI82871
Volmer, R., van der Ploeg, K. & Ron, D. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl Acad. Sci. USA 110, 4628–4633 (2013).
pubmed: 23487760
pmcid: 3606975
doi: 10.1073/pnas.1217611110
Halbleib, K. et al. Activation of the unfolded protein response by lipid bilayer stress. Mol. Cell 67, 673–684.e8 (2017).
pubmed: 28689662
doi: 10.1016/j.molcel.2017.06.012
Chitraju, C. et al. Triglyceride synthesis by DGAT1 protects adipocytes from lipid-induced ER stress during lipolysis. Cell Metab. 26, 407–418.e3 (2017).
pubmed: 28768178
pmcid: 6195226
doi: 10.1016/j.cmet.2017.07.012
Listenberger, L. L. et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl Acad. Sci. USA 100, 3077–3082 (2003).
pubmed: 12629214
pmcid: 152249
doi: 10.1073/pnas.0630588100
Otten, E. G. et al. Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection. Nature 594, 111–116 (2021).
pubmed: 34012115
pmcid: 7610904
doi: 10.1038/s41586-021-03566-4
Sugihara, M. et al. The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets. J. Cell Biol. 218, 949–960 (2019).
pubmed: 30705059
pmcid: 6400562
doi: 10.1083/jcb.201712120
Senkal, C. E. et al. Ceramide is metabolized to acylceramide and stored in lipid droplets. Cell Metab. 25, 686–697 (2017).
pubmed: 28273483
pmcid: 5472424
doi: 10.1016/j.cmet.2017.02.010
Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22, 266–282 (2021).
pubmed: 33495651
pmcid: 8142022
doi: 10.1038/s41580-020-00324-8
Li, Z., Lange, M., Dixon, S. J. & Olzmann, J. A. Lipid quality control and ferroptosis: from concept to mechanism. Annu. Rev. Biochem. https://doi.org/10.1146/annurev-biochem-052521-033527 (2024).
doi: 10.1146/annurev-biochem-052521-033527
Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317–331 (2014).
pubmed: 24439385
pmcid: 4076414
doi: 10.1016/j.cell.2013.12.010
Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698 (2019).
pubmed: 31634899
doi: 10.1038/s41586-019-1707-0
Bersuker, K. et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692 (2019).
pubmed: 31634900
pmcid: 6883167
doi: 10.1038/s41586-019-1705-2
Mishima, E. et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608, 778–783 (2022).
pubmed: 35922516
pmcid: 9402432
doi: 10.1038/s41586-022-05022-3
Jin, D.-Y. et al. A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. Nat. Commun. 14, 828 (2023).
pubmed: 36788244
pmcid: 9929328
doi: 10.1038/s41467-023-36446-8
Danielli, M., Perne, L., Jarc Jovičić, E. & Petan, T. Lipid droplets and polyunsaturated fatty acid trafficking: balancing life and death. Front. Cell Dev. Biol. 11, 1104725 (2023).
pubmed: 36776554
pmcid: 9911892
doi: 10.3389/fcell.2023.1104725
Doll, S. et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol. 13, 91–98 (2017).
pubmed: 27842070
doi: 10.1038/nchembio.2239
Magtanong, L. et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem. Biol. 26, 420–432.e9 (2019).
pubmed: 30686757
pmcid: 6430697
doi: 10.1016/j.chembiol.2018.11.016
Dierge, E. et al. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 33, 1701–1715.e5 (2021).
pubmed: 34118189
doi: 10.1016/j.cmet.2021.05.016
Ioannou, M. S. et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell 177, 1522–1535.e14 (2019).
pubmed: 31130380
doi: 10.1016/j.cell.2019.04.001
Minami, J. K. et al. CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis. Cancer Cell 41, 1048–1060.e9 (2023).
pubmed: 37236196
doi: 10.1016/j.ccell.2023.05.001
Bailey, A. P. et al. Antioxidant role for lipid droplets in a stem cell niche of drosophila. Cell 163, 340–353 (2015).
pubmed: 26451484
pmcid: 4601084
doi: 10.1016/j.cell.2015.09.020
Ralhan, I. et al. Autolysosomal exocytosis of lipids protect neurons from ferroptosis. J. Cell Biol. 222, e202207130 (2023).
pubmed: 37036445
pmcid: 10098143
doi: 10.1083/jcb.202207130
Mohammadyani, D. et al. Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: mass spectrometry and coarse-grained simulations. Free Radic. Biol. Med 76, 53–60 (2014).
pubmed: 25110833
pmcid: 4276254
doi: 10.1016/j.freeradbiomed.2014.07.042
Ferrada, L., Barahona, M. J., Vera, M., Stockwell, B. R. & Nualart, F. Dehydroascorbic acid sensitizes cancer cells to system x
Zou, Y. et al. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat. Commun. 10, 1617 (2019).
pubmed: 30962421
pmcid: 6453886
doi: 10.1038/s41467-019-09277-9
Roberts, M. A. et al. Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation. Dev. Cell 58, 1782–1800.e10 (2023).
pubmed: 37494933
doi: 10.1016/j.devcel.2023.07.001
Mejhert, N. et al. The Lipid Droplet Knowledge Portal: a resource for systematic analyses of lipid droplet biology. Dev. Cell 57, 387–397.e4 (2022).
pubmed: 35134345
pmcid: 9129885
doi: 10.1016/j.devcel.2022.01.003
Wang, L. et al. Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy. Cell Biosci. 10, 55 (2020).
pubmed: 32280452
pmcid: 7137450
doi: 10.1186/s13578-020-00414-2
Prévost, C. et al. Mechanism and determinants of amphipathic helix-containing protein targeting to lipid droplets. Dev. Cell 44, 73–86.e4 (2018).
pubmed: 29316443
pmcid: 5764114
doi: 10.1016/j.devcel.2017.12.011
Chorlay, A. & Thiam, A. R. Neutral lipids regulate amphipathic helix affinity for model lipid droplets. J. Cell Biol. 219, e201907099 (2020).
pubmed: 32328636
pmcid: 7147095
doi: 10.1083/jcb.201907099
Wolins, N. E., Brasaemle, D. L. & Bickel, P. E. A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett. 580, 5484–5491 (2006).
pubmed: 16962104
doi: 10.1016/j.febslet.2006.08.040
Kim, S., Swanson, J. M. J. & Voth, G. A. Computational studies of lipid droplets. J. Phys. Chem. B 126, 2145–2154 (2022).
pubmed: 35263109
pmcid: 8957551
doi: 10.1021/acs.jpcb.2c00292
Chen, F., Yin, Y., Chua, B. T. & Li, P. CIDE family proteins control lipid homeostasis and the development of metabolic diseases. Traffic 21, 94–105 (2020).
pubmed: 31746121
doi: 10.1111/tra.12717
Lyu, X. et al. A gel-like condensation of Cidec generates lipid-permeable plates for lipid droplet fusion. Dev. Cell 56, 2592–2606.e7 (2021).
pubmed: 34508658
doi: 10.1016/j.devcel.2021.08.015
Qian, K. et al. CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization. Nature 613, 160–168 (2023).
pubmed: 36477540
doi: 10.1038/s41586-022-05507-1
Sharma, A. K. & Wolfrum, C. Lipid cycling isn’t all futile. Nat. Metab. 5, 540–541 (2023).
pubmed: 37012497
doi: 10.1038/s42255-023-00779-x
Wunderling, K., Zurkovic, J., Zink, F., Kuerschner, L. & Thiele, C. Triglyceride cycling enables modification of stored fatty acids. Nat. Metab. 5, 699–709 (2023).
pubmed: 37012495
pmcid: 10132980
doi: 10.1038/s42255-023-00769-z
Patel, R. et al. ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty acids. Nature 606, 968–975 (2022).
pubmed: 35676490
pmcid: 9242854
doi: 10.1038/s41586-022-04787-x
Yore, M. M. et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318–332 (2014).
pubmed: 25303528
pmcid: 4260972
doi: 10.1016/j.cell.2014.09.035
Schulze, R. J. et al. Direct lysosome-based autophagy of lipid droplets in hepatocytes. Proc. Natl Acad. Sci. USA 117, 32443–32452 (2020).
Menon, D. et al. ARL8B mediates lipid droplet contact and delivery to lysosomes for lipid remobilization. Cell Rep. 42, 113203 (2023).
pubmed: 37777960
doi: 10.1016/j.celrep.2023.113203
Omrane, M. et al. LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy. Dev. Cell 58, 1266–1281.e7 (2023).
pubmed: 37315562
doi: 10.1016/j.devcel.2023.05.009