Inhibition of dipeptidyl peptidase 7 impairs lysophagy in LLOMe-treated HepG2 cells.

Authors

Na Yeon Park, Inho Kwon, Yong Hwan Kim, Ji-Eun Bae, Joon Bum Kim, Seong Hyun Kim, Sungho Maeng, Doo Sin Jo, Dong-Hyung Cho

Published in

FEBS letters. Oct 08, 2026. Epub Oct 08, 2026.

Abstract

Lysophagy selectively eliminates damaged lysosomes to preserve lysosomal homeostasis, but its regulatory mechanisms remain incompletely understood. Here, we identify dipeptidyl peptidase 7 (DPP7), a lysosomal serine protease, as a regulator of lysophagy. Inhibition or depletion of DPP7 impaired clearance of LLOMe-damaged lysosomes in HepG2 cells, as evidenced by sustained galectin-3 puncta and reduced lysophagic flux. DPP7 inhibition did not block TFEB activation; however, it markedly reduced ubiquitin accumulation on damaged lysosomes and attenuated the recruitment of SQSTM1 and LC3. This defect was accompanied by impaired lysosomal re-acidification and reduced maturation of cathepsin D and L. Together, our findings identify DPP7 as a novel modulator of ubiquitin-dependent lysophagy and reveal an unexpected role for a lysosomal peptidase in lysosomal quality control.

PMID:
42850984
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.