Cvm1 is a component of multiple vacuolar contact sites required for sphingolipid homeostasis

Author:

Bisinski Daniel D.1ORCID,Gomes Castro Inês2ORCID,Mari Muriel3ORCID,Walter Stefan4,Fröhlich Florian45ORCID,Schuldiner Maya2ORCID,González Montoro Ayelén14ORCID

Affiliation:

1. Department of Biology/Chemistry, Cellular Communication Laboratory, University of Osnabrück, Osnabrück, Germany 1

2. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel 2

3. Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, Netherlands 3

4. Center of Cellular Nanoanalytics Osnabrück, Osnabrück, Germany 4

5. Department of Biology/Chemistry, Molecular Membrane Biology Group, University of Osnabrück, Osnabrück, Germany 5

Abstract

Membrane contact sites are specialized platforms formed between most organelles that enable them to exchange metabolites and influence the dynamics of each other. The yeast vacuole is a degradative organelle equivalent to the lysosome in higher eukaryotes with important roles in ion homeostasis and metabolism. Using a high-content microscopy screen, we identified Ymr160w (Cvm1, for contact of the vacuole membrane 1) as a novel component of three different contact sites of the vacuole: with the nuclear endoplasmic reticulum, the mitochondria, and the peroxisomes. At the vacuole–mitochondria contact site, Cvm1 acts as a tether independently of previously known tethers. We show that changes in Cvm1 levels affect sphingolipid homeostasis, altering the levels of multiple sphingolipid classes and the response of sphingolipid-sensing signaling pathways. Furthermore, the contact sites formed by Cvm1 are induced upon a decrease in sphingolipid levels. Altogether, our work identifies a novel protein that forms multiple contact sites and supports a role of lysosomal contacts in sphingolipid homeostasis.

Funder

Schering and Fritz Thyssen Foundations

Deutsche Forschungsgemeinschaft

Volkswagen Foundation

European Molecular Biology Organization

Dutch Research Council

Publisher

Rockefeller University Press

Subject

Cell Biology

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