Lysosomal Ca2+ release channel TRPML1 regulates lysosome size by promoting mTORC1 activity.

Abstract:

:Lysosomal Ca2+ release channel TRPML1 has been suggested to regulate lysosome size by activating calmodulin (CaM). To further understand how TRPML1 and CaM regulate lysosome size, in this study, we report that inhibiting mTORC1 causes enlarged lysosomes, and the recovery of enlarged lysosomes is suppressed by inhibiting mTORC1. We also show that lysosome vacuolation induced by inhibiting TRPML1 is corrected by mTORC1 upregulation, and the facilitating effect of TRPML1 on the recovery of enlarged lysosomes is suppressed by inhibiting mTORC1. In the meantime, lysosome vacuolation induced by inhibiting CaM is corrected by mTORC1 upregulation, and mTORC1 overexpression corrects the inhibitory effect of CaM antagonist on the recovery of enlarged lysosomes. Conversely, the vacuolation induced by suppressing mTORC1 is not corrected by upregulating CaM. These data suggest that mTORC1 functions downstream of TRPML1 and CaM to regulate lysosome size. Together with our recent finding showing that TRPML1, CaM and mTORC1 form a macromolecular complex to control mTORC1 activity, we suggest that TRPML1 and CaM control lysosome fission through regulating mTORC1, identifying an mTORC1-dependent molecular mechanism for lysosomal membrane fission.

journal_name

Eur J Cell Biol

authors

Yang Y,Xu M,Zhu X,Yao J,Shen B,Dong XP

doi

10.1016/j.ejcb.2019.05.001

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

116-123

issue

2-4

eissn

0171-9335

issn

1618-1298

pii

S0171-9335(18)30183-3

journal_volume

98

pub_type

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