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Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1
- Source :
- Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science Advances, 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science advances, Vol. 7, No 46 (2021) P. eabe5469
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- Description<br />RECS1, a member of the TMBIM family, triggers lysosomal membrane permeabilization in cells undergoing lysosomal stress.<br />Programmed cell death is regulated by the balance between activating and inhibitory signals. Here, we have identified RECS1 (responsive to centrifugal force and shear stress 1) [also known as TMBIM1 (transmembrane BAX inhibitor motif containing 1)] as a proapoptotic member of the TMBIM family. In contrast to other proteins of the TMBIM family, RECS1 expression induces cell death through the canonical mitochondrial apoptosis pathway. Unbiased screening indicated that RECS1 sensitizes cells to lysosomal perturbations. RECS1 localizes to lysosomes, where it regulates their acidification and calcium content, triggering lysosomal membrane permeabilization. Structural modeling and electrophysiological studies indicated that RECS1 is a pH-regulated calcium channel, an activity that is essential to trigger cell death. RECS1 also sensitizes whole animals to stress in vivo in Drosophila melanogaster and zebrafish models. Our results unveil an unanticipated function for RECS1 as a proapoptotic component of the TMBIM family that ignites cell death programs at lysosomes.
- Subjects :
- Programmed cell death
STRESS
BI-1
[SDV]Life Sciences [q-bio]
MEMBRANE PERMEABILIZATION
Ph dependent
ddc:616.07
ANTI-APOPTOTIC PROTEINS
Inhibitory postsynaptic potential
CA2+
03 medical and health sciences
0302 clinical medicine
FLUORESCENCE
ddc:612
030304 developmental biology
0303 health sciences
Multidisciplinary
UNFOLDED PROTEIN RESPONSE
Chemistry
Calcium channel
SciAdv r-articles
Life Sciences
Cell Biology
NEGATIVE REGULATOR
Cell biology
[SDV] Life Sciences [q-bio]
BAX INHIBITOR-1
ER
030220 oncology & carcinogenesis
1182 Biochemistry, cell and molecular biology
Biomedicine and Life Sciences
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23752548
- Database :
- OpenAIRE
- Journal :
- Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science Advances, 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science advances, Vol. 7, No 46 (2021) P. eabe5469
- Accession number :
- edsair.doi.dedup.....8206126f35066a19b6c7861afb35003f
- Full Text :
- https://doi.org/10.1126/sciadv.abe5469⟩