LIPID BIOLOGY

Going through a phase

Genetic screens uncover a bioactivation pathway for Lasonolide A involving enrichment in lipid droplets and cleavage into a cytotoxic, soluble metabolite by a lipid droplet-associated serine hydrolase. These findings identify enzymatically regulated phase partitioning as a drug activation mechanism.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Enzymatic processing by the ER and lipid droplet localized hydrolase LDAH controls LasA phase partitioning and cytotoxicity.

References

  1. 1.

    Walther, T. C., Chung, J. & Farese, R. V. Jr. Annu. Rev. Cell Dev. Biol. 33, 491–510 (2017).

  2. 2.

    Olzmann, J. A. & Carvalho, P. Nat. Rev. Mol. Cell Biol. 20, 137–155 (2019).

  3. 3.

    Dubey, R. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-019-0447-7 (2020).

  4. 4.

    Isbrucker, R. A., Guzmán, E. A., Pitts, T. P. & Wright, A. E. J. Pharmacol. Exp. Ther. 331, 733–739 (2009).

  5. 5.

    Horton, P. A., Koehn, F. E., Longley, R. E. & McConnell, O. J. J. Am. Chem. Soc. 116, 6015–6016 (1994).

  6. 6.

    Zhang, Y.-W., Ghosh, A. K. & Pommier, Y. Cell Cycle 11, 4424–4435 (2012).

  7. 7.

    Goo, Y.-H., Son, S.-H., Kreienberg, P. B. & Paul, A. Arterioscler. Thromb. Vasc. Biol. 34, 386–396 (2014).

  8. 8.

    Goo, Y.-H., Son, S.-H. & Paul, A. Sci. Rep. 7, 2743 (2017).

  9. 9.

    Kory, N. et al. J. Lipid Res. 58, 226–235 (2017).

  10. 10.

    Greenwood, D. J. et al. Science 364, 1279–1282 (2019).

Download references

Author information

Correspondence to James A. Olzmann.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Morris, S.N.S. & Olzmann, J.A. Going through a phase. Nat Chem Biol (2020) doi:10.1038/s41589-019-0448-6

Download citation