Clearing debris

A new small molecule that targets the vacuolar H+-ATPase activates autophagy, inhibits mTORC1 signaling, and displays potential for clearing toxic protein aggregates involved in neurodegenerative diseases.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: EN6 promotes autophagy by enhancing vacuolar H+-ATPase (v-ATPase) activity and inhibiting mTORC1 signaling.


  1. 1.

    Choi, A. M., Ryter, S. W. & Levine, B. N. Engl. J. Med. 368, 651–662 (2013).

    CAS  Article  Google Scholar 

  2. 2.

    Harris, H. & Rubinsztein, D. C. Nat. Rev. Neurol. 8, 108–117 (2011).

    Article  Google Scholar 

  3. 3.

    Jewell, J. L., Russell, R. C. & Guan, K. L. Nat. Rev. Mol. Cell Biol. 14, 133–139 (2013).

    CAS  Article  Google Scholar 

  4. 4.

    Lawrence, R. E. & Zoncu, R. Nat. Cell Biol. 21, 133–142 (2019).

    CAS  Article  Google Scholar 

  5. 5.

    Chung, C. Y. et al. Nat. Chem. Biol. (2019).

  6. 6.

    Zoncu, R. et al. Science 334, 678–683 (2011).

    CAS  Article  Google Scholar 

  7. 7.

    Saxton, R. A. & Sabatini, D. M. Cell 168, 960–976 (2017).

    CAS  Article  Google Scholar 

  8. 8.

    Okosun, J. et al. Nat. Genet. 48, 183–188 (2016).

    CAS  Article  Google Scholar 

  9. 9.

    Wang, F. et al. J. Clin. Invest. 130, 1626–1640 (2019).

    Article  Google Scholar 

  10. 10.

    Galluzzi, L., Bravo-San Pedro, J. M., Demaria, S., Formenti, S. C. & Kroemer, G. Nat. Rev. Clin. Oncol. 14, 247–258 (2017).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Jenna L. Jewell.

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

Meng, D., Jewell, J.L. Clearing debris. Nat Chem Biol 15, 760–761 (2019).

Download citation


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing