The Vps13-like protein BLTP2 regulates phosphatidylethanolamine levels to maintain plasma membrane fluidity and breast cancer aggressiveness.

Lipid transport proteins (LTPs) facilitate non-vesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis. A recently identified family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles. One of these, BLTP2, is conserved across species but its function is not known.

Recent Contributions of Mass Spectrometry-Based "Omics" in the Studies of Breast Cancer.

Breast cancer (BC) is one of the most heterogeneous groups of cancer. As every biotype of BC is unique and presents a particular "omic" signature, they are increasingly characterized nowadays with novel mass spectrometry (MS) strategies. BC therapeutic approaches are primarily based on the two features of human epidermal growth factor receptor 2 (HER2) and estrogen receptor (ER) positivity.

Early steps in the birth of four membrane-bound organelles-Peroxisomes, lipid droplets, lipoproteins, and autophagosomes.

Membrane-bound organelles allow cells to traffic cargo and separate and regulate metabolic pathways. While many organelles are generated by the growth and division of existing organelles, some can also be produced de novo, often in response to metabolic cues. This review will discuss recent advances in our understanding of the early steps in the de novo biogenesis of peroxisomes, lipid droplets, lipoproteins, and autophagosomes.

Vps13-like proteins provide phosphatidylethanolamine for GPI anchor synthesis in the ER.

Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor requires three molecules of ethanolamine phosphate (P-Etn), which are derived from phosphatidylethanolamine (PE).

Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids.

Luminal pH and the distinctive distribution of phosphatidylinositol phosphate (PIP) lipids are central identifying features of organelles in all eukaryotic cells that are also critical for organelle function. V-ATPases are conserved proton pumps that populate and acidify multiple organelles of the secretory and the endocytic pathway. Complete loss of V-ATPase activity causes embryonic lethality in higher animals and conditional lethality in yeast, while partial loss of V-ATPase function is associated with multiple disease states.

Interaction of the late endo-lysosomal lipid PI(3,5)P2 with the Vph1 isoform of yeast V-ATPase increases its activity and cellular stress tolerance.

The low-level endo-lysosomal signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), is required for full assembly and activity of vacuolar H-ATPases (V-ATPases) containing the vacuolar a-subunit isoform Vph1 in yeast. The cytosolic N-terminal domain of Vph1 is also recruited to membranes in a PI(3,5)P2-dependent manner, but it is not known if its interaction with PI(3,5)P2 is direct. Here, using biochemical characterization of isolated yeast vacuolar vesicles, we demonstrate that addition of exogenous short-chain PI(3,5)P2 to Vph1-containing vacuolar vesicles activates V-ATPase activity and proton pumping.

Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast.

Luminal pH and phosphoinositide content are fundamental features of organelle identity. Vacuolar H-ATPases (V-ATPases) drive organelle acidification in all eukaryotes, and membrane-bound a-subunit isoforms of the V-ATPase are implicated in organelle-specific targeting and regulation. Earlier work demonstrated that the endolysosomal lipid PI(3,5)P activates V-ATPases containing the vacuolar a-subunit isoform in Here we demonstrate that PI(4)P, the predominant Golgi phosphatidylinositol (PI) species, directly interacts with the cytosolic amino terminal (NT) domain of the yeast Golgi V-ATPase a-isoform Stv1.