bims-mecosi 2022-05-22 papers

Issue of 2022–05–22
four papers selected by
Verena Kohler, Stockholm University

Front Cell Dev Biol. 2022 ;10 867341

The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.

Elizabeth G Hunt, Alex M Andrews, Sydney R Larsen, Jessica E Thaxton.

The endoplasmic reticulum (ER) is a large continuous membranous organelle that plays a central role as the hub of protein and lipid synthesis while the mitochondria is the principal location for energy production. T cells are an immune subset exhibiting robust dependence on ER and mitochondrial function based on the need for protein synthesis and secretion and metabolic dexterity associated with foreign antigen recognition and cytotoxic effector response. Intimate connections exist at mitochondrial-ER contact sites (MERCs) that serve as the structural and biochemical platforms for cellular metabolic homeostasis through regulation of fission and fusion as well as glucose, Ca2+, and lipid exchange. Work in the tumor immunotherapy field indicates that the complex interplay of nutrient deprivation and tumor antigen stimulation in the tumor microenvironment places stress on the ER and mitochondria, causing dysfunction in organellar structure and loss of metabolic homeostasis. Here, we assess prior literature that establishes how the structural interface of these two organelles is impacted by the stress of solid tumors along with recent advances in the manipulation of organelle homeostasis at MERCs in T cells. These findings provide strong evidence for increased tumor immunity using unique therapeutic avenues that recharge cellular metabolic homeostasis in T cells.

Keywords: ER stress; MERCs; T cell; cancer immunotherapy; endoplasmic recticulum (ER); metabolism; tumor microenvironment

DOI: https://doi.org/10.3389/fcell.2022.867341

Curr Opin Cell Biol. 2022 May 12. pii: S0955-0674(22)00031-X. [Epub ahead of print]76 102085

Protein control of membrane and organelle dynamics: Insights from the divergent eukaryote Toxoplasma gondii.

Jana Ovciarikova, Rodolpho Ornitz Oliveira Souza, Gustavo Arrizabalaga, Lilach Sheiner.

Integral membrane protein complexes control key cellular functions in eukaryotes by defining membrane-bound spaces within organelles and mediating inter-organelles contacts. Despite the critical role of membrane complexes in cell biology, most of our knowledge is from a handful of model systems, primarily yeast and mammals, while a full functional and evolutionary understanding remains incomplete without the perspective from a broad range of divergent organisms. Apicomplexan parasites are single-cell eukaryotes whose survival depends on organelle compartmentalisation and communication. Studies of a model apicomplexan, Toxoplasma gondii, reveal unexpected divergence in the composition and function of complexes previously considered broadly conserved, such as the mitochondrial ATP synthase and the tethers mediating ER-mitochondria membrane contact sites. Thus, Toxoplasma joins the repertoire of divergent model eukaryotes whose research completes our understanding of fundamental cell biology.

DOI: https://doi.org/10.1016/j.ceb.2022.102085

New Phytol. 2022 May 19.

Phosphatidylinositol 4-phosphate: a key determinant of plasma membrane identity and function in plants.

Vedrana Marković, Yvon Jaillais.

Phosphatidylinositol 4-phosphate (PI4P) is an anionic phospholipid, which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all plant cells analyzed so far. Besides, many functions that are typically attributed to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ] in animal and yeast cells are also supported by PI4P in plants. For example, PI4P is the key anionic lipid that powers the strong electrostatic properties of the plasma membrane. PI4P is also required for the establishment of stable membrane contacts between the endoplasmic reticulum (ER) and the plasma membrane, for exocytosis and to support signaling pathways. Thus, we propose that PI4P has a prominent role in specifying the identity of the plasma membrane and in supporting some of its key functions and should be considered a hallmark lipid of this compartment.

Keywords: PtdIns4P; endocytosis; membrane contact sites; membrane lipid; nanodomains; phosphoinositides; plant cell biology; trafficking

DOI: https://doi.org/10.1111/nph.18258

Nat Rev Mol Cell Biol. 2022 May 19.

Phosphoinositides as membrane organizers.

York Posor, Wonyul Jang, Volker Haucke.

Phosphoinositides are signalling lipids derived from phosphatidylinositol, a ubiquitous phospholipid in the cytoplasmic leaflet of eukaryotic membranes. Initially discovered for their roles in cell signalling, phosphoinositides are now widely recognized as key integrators of membrane dynamics that broadly impact on all aspects of cell physiology and on disease. The past decade has witnessed a vast expansion of our knowledge of phosphoinositide biology. On the endocytic and exocytic routes, phosphoinositides direct the inward and outward flow of membrane as vesicular traffic is coupled to the conversion of phosphoinositides. Moreover, recent findings on the roles of phosphoinositides in autophagy and the endolysosomal system challenge our view of lysosome biology. The non-vesicular exchange of lipids, ions and metabolites at membrane contact sites in between organelles has also been found to depend on phosphoinositides. Here we review our current understanding of how phosphoinositides shape and direct membrane dynamics to impact on cell physiology, and provide an overview of emerging concepts in phosphoinositide regulation.

DOI: https://doi.org/10.1038/s41580-022-00490-x