Membrane contact sites are regions where organelle membranes come together, and serve as platforms for metabolite exchange, process organization, and regulation of organelle dynamics. The yeast vacuole, equivalent to lysosomes in higher eukaryotes, functions as a degradative organelle, storage compartment, and signaling hub, establishing contacts with multiple organelles. We previously identified the protein Cvm1 as a component of vacuole contact sites with mitochondria, the nuclear endoplasmic reticulum, and peroxisomes. Here, we investigate Cvm1-mediated contacts and show that the contacts with mitochondria require the porins Por1 and Por2. Additionally, Cvm1 forms a protein complex with its paralog Yml020w, which we designate as Cvm2. Bioinformatic analysis predicts that both proteins contain an α/β-hydrolase fold. Notably, the predicted catalytic triad of Cvm2 is essential for its in vivo function, while Cvm1 lacks an active site. Complex formation is necessary for the function of the proteins, and Cvm1 targets the complex to the vacuole by binding phosphatidylinositol-3-phosphate on this membrane. Overexpression of this complex generates extended contacts between the vacuole and the peripheral endoplasmic reticulum. Collectively, our work describes the novel Cvm1-Cvm2 complex and molecular interactions important for its function as part of vacuolar contact sites. [Media: see text].

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Journal Article

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Bisinski DD, Klössel S, Rasche R, Breitsprecher L, Gehle N, Psathaki OE, Quiroga R, Kümmel D, Montoro AG

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