Lysosomal ATP Transporter SLC17A9 Controls Cell Viability via Regulating Cathepsin D

SLC17A9 (solute carrier family 17 member 9) functions as an ATP transporter in lysosomes as well as other secretory vesicles. SLC17A9 inhibition or silence leads to cell death. However, the molecular mechanisms causing cell death are unclear. In this study, we report that cell death induced by SLC17...

Full description

Saved in:
Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2022-03, Vol.11 (5), p.887
Main Authors: Huang, Peng, Cao, Qi, Xu, Mengnan, Dong, Xian-Ping
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Antibodies
Apoptosis
Aspartic endopeptidase
ATP transporter
Cathepsin B
Cathepsin B - genetics
Cathepsin B - metabolism
Cathepsin D
Cathepsin D - genetics
Cathepsin D - metabolism
Cell death
Cell Survival
Cell viability
Cloning
Cysteine proteinase
Enzymes
Experiments
Lysosomal protein
lysosome
Lysosomes
Lysosomes - metabolism
Membrane Transport Proteins - metabolism
Membranes
Microscopy
Molecular modelling
Nucleotide Transport Proteins - genetics
Plasmids
Proteins
Secretory vesicles
solute carrier family 17 member 9 (SLC17A9)
Stains & staining
vesicular nucleotide transporter (VNUT)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:SLC17A9 (solute carrier family 17 member 9) functions as an ATP transporter in lysosomes as well as other secretory vesicles. SLC17A9 inhibition or silence leads to cell death. However, the molecular mechanisms causing cell death are unclear. In this study, we report that cell death induced by SLC17A9 deficiency is rescued by the transcription factor EB (TFEB), a master gene for lysosomal protein expression, suggesting that SLC17A9 deficiency may be the main cause of lysosome dysfunction, subsequently leading to cell death. Interestingly, Cathepsin D, a lysosomal aspartic protease, is inhibited by SLC17A9 deficiency. Heterologous expression of Cathepsin D successfully rescues lysosomal dysfunction and cell death induced by SLC17A9 deficiency. On the other hand, the activity of Cathepsin B, a lysosomal cysteine protease, is not altered by SLC17A9 deficiency, and Cathepsin B overexpression does not rescue lysosomal dysfunction and cell death induced by SLC17A9 deficiency. Our data suggest that lysosomal ATP and SLC17A9 play critical roles in lysosomal function and cell viability by regulating Cathepsin D activity.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11050887