title: SLC17A9 protein functions as a lysosomal ATP transporter and regulates cell viability.
abstract: Lysosomes contain abundant ATP, which is released through lysosomal exocytosis following exposure to various stimuli. However, the molecular mechanisms underlying lysosomal ATP accumulation remain unknown. The vesicular nucleotide transporter, also known as solute carrier family 17 member 9 (SLC17A9), has been shown to function in ATP transport across secretory vesicles/granules membrane in adrenal chromaffin cells, T cells, and pancreatic cells. Here, using mammalian cell lines, we report that SLC17A9 is highly enriched in lysosomes and functions as an ATP transporter in those organelles. SLC17A9 deficiency reduced lysosome ATP accumulation and compromised lysosome function, resulting in cell death. Our data suggest that SLC17A9 activity mediates lysosomal ATP accumulation and plays an important role in lysosomal physiology and cell viability.
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Qi
authors: Q
authors: Cao
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Kexin
authors: K
authors: Zhao
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Xi Zoë
authors: XZ
authors: Zhong
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Yuanjie
authors: Y
authors: Zou
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Haichuan
authors: H
authors: Yu
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and.
authors: Peng
authors: P
authors: Huang
authors: Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Tian-Le
authors: TL
authors: Xu
authors: Department of Physiology and Biophysics, Dalhousie University, Halifax B3H 4R2, Nova Scotia, Canada and. Electronic address: xpdong@dal.ca.
authors: Xian-Ping
authors: XP
authors: Dong
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D019556:COS Cells; D016923:Cell Death; D002470:Cell Survival / Q000502:physiology; D002522:Chlorocebus aethiops; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D033704:Nucleotide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D033704:Nucleotide Transport Proteins; C529437:Slc17a9 protein, human; D000255:Adenosine Triphosphate
keywords: ATP; Cell Death; Lysosome; Transporter; Vacuolar ATPase; Vesicular Nucleotide Transporter