Evidence map›Paper›PMID 40473625›Full record

ArticleNature communications2025

Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal Ca

Ran Chen, Bin Liu, Dawid Jaślan, Lucija Kucej, Veronika Kudrina, Belinda Warnke, Yvonne E Klingl, Arnas Petrauskas, Sandra Prat Castro, Kenji Maeda and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ran Chen *Cell Death and Metabolism, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Institute, Copenhagen, Denmark.ORCID http://orcid.org/0009-0008-1185-629X
Bin Liu *Cell Death and Metabolism, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Institute, Copenhagen, Denmark. ubnl@novonordisk.com.ORCID http://orcid.org/0000-0001-7489-9125
Dawid Jaślan *Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0002-0685-7633
Lucija KucejCell Death and Metabolism, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Institute, Copenhagen, Denmark.ORCID http://orcid.org/0009-0000-1982-6919
Veronika KudrinaWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0002-3762-8673
Belinda WarnkeWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Yvonne E KlinglWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0003-2779-3357
Arnas PetrauskasWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0001-9048-582X
Sandra Prat CastroWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID http://orcid.org/0000-0002-1007-2839
Kenji MaedaCell Death and Metabolism, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Institute, Copenhagen, Denmark.
Christian GrimmWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany. christian.grimm@med.uni-muenchen.de.ORCID http://orcid.org/0000-0002-0177-5559
Marja JäätteläCell Death and Metabolism, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Institute, Copenhagen, Denmark. mj@cancer.dk.ORCID http://orcid.org/0000-0001-5950-7111

Funding

Danmarks Grundforskningsfond (Danish National Research Foundation) DNRF125Deutsche Forschungsgemeinschaft (German Research Foundation) GR4315/7-1Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1328 A21Deutsche Forschungsgemeinschaft (German Research Foundation) SFB/TRR152 P04Novo Nordisk Fonden (Novo Nordisk Foundation) NNF19OC0054296
6 · The paper itself

Abstract

The proper function of lysosomes depends on their ability to store and release calcium. While several lysosomal calcium release channels have been described, how lysosomes replenish their calcium stores in placental mammals has not been determined. Using genetic depletion and overexpression techniques combined with electrophysiology and visualization of subcellular ion concentrations and their fluxes across the lysosomal membrane, we show here that TMEM165 imports calcium to the lysosomal lumen and mediates calcium-induced lysosomal proton leakage. Accordingly, TMEM165 accelerates the recovery of cells from cytosolic calcium overload thereby enhancing cell survival while causing a significant acidification of the cytosol. These data indicate that in addition to its previously identified role in the glycosylation of proteins and lipids in the Golgi, a fraction of TMEM165 localizes on the lysosomal limiting membrane, where its putative calcium/proton antiporter activity plays an essential role in the regulation of intracellular ion homeostasis and cell survival.

Indexed as

AntiportersCalciumLysosomesAnimalsCell SurvivalCytosolGolgi ApparatusHEK293 CellsHeLa CellsHomeostasisHumansHydrogen-Ion ConcentrationIon TransportProtonsAntiportersCalciumProtons

Identifiers

PMID40473625
PMCPMC12141690

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.