bims-mecosi 2022-01-30 papers

Issue of 2022‒01‒30
four papers selected by
Verena Kohler

Mol Biol (Mosk). 2022 Jan-Feb;56(1):56(1): 69-82

[Molecular Mechanisms of Interactions between Mitochondria and the Endoplasmic Reticulum: A New Look at How Important Cell Functions are Supported].

V S Sukhorukov, A S Voronkova, T I Baranich, A A Gofman, A V Brydun, L A Knyazeva, V V Glinkina.

Interactions between the endoplasmic reticulum (ER) and mitochondria have received insufficient attention until recently. However, distorted contacts between the ER and mitochondria were identified as an important factor in the etiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In view of these new data, the mechanisms of ER-mitochondrial interactions are necessary to study in detail in order to develop new diagnostic and therapeutic approaches to neurodegenerative diseases and to extend basic knowledge of the physiology of the eukaryotic cell. The review focuses on the functions of mitochondria-associated ER membranes (MAMs). Structural elements of the MAM system, their contributions to the vital cell functions (calcium and lipid homeostasis, autophagy, fusion and division of mitochondria, and the regulation of their number), and the role of MAM dysfunctions in the pathogenesis of various neurodegenerative diseases are considered.

Keywords: calcium; chaperone; endoplasmic reticulum; membrane; mitochondria; neurodegenerative diseases

DOI: https://doi.org/10.31857/S0026898422010098

Contact (Thousand Oaks). 2021 Jan 01. 4 1-15

The Fast and the Furious: Golgi Contact Sites.

Yotam David, Inês G Castro, Maya Schuldiner.

Contact sites are areas of close apposition between two membranes that coordinate nonvesicular communication between organelles. Such interactions serve a wide range of cellular functions from regulating metabolic pathways to executing stress responses and coordinating organelle inheritance. The past decade has seen a dramatic increase in information on certain contact sites, mostly those involving the endoplasmic reticulum. However, despite its central role in the secretory pathway, the Golgi apparatus and its contact sites remain largely unexplored. In this review, we discuss the current knowledge of Golgi contact sites and share our thoughts as to why Golgi contact sites are understudied. We also highlight what exciting future directions may exist in this emerging field.

Keywords: Golgi; PI4P; cholesterol; contact sites; oxysterol-binding protein (OSBP); phosphoinositide

DOI: https://doi.org/10.1177/25152564211034424

Front Cell Dev Biol. 2021 ;9 797949

Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation.

Carlos Enrich, Albert Lu, Francesc Tebar, Carles Rentero, Thomas Grewal.

Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10-30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this "Mini Review" we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.

Keywords: annexins; calcium-binding proteins; cholesterol; endolysosomes; endoplasmic reticulum; lipid transport; membrane contact sites; mitochondria

DOI: https://doi.org/10.3389/fcell.2021.797949

J Biol Chem. 2022 Jan 20. pii: S0021-9258(22)00047-3. [Epub ahead of print] 101607

The mammalian trafficking chaperone protein UNC93B1 maintains the ER calcium sensor STIM1 in a dimeric state primed for translocation to the ER cortex.

Wen-An Wang, Nicolas Demaurex.

The stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum (ER) Ca2+ sensor that regulates the activity of Orai plasma membrane Ca2+ channels to mediate the store-operated Ca2+ entry (SOCE) pathway essential for immunity. Unc-93 homologue B1 (UNC93B1) is a multiple membrane-spanning ER protein that acts as a trafficking chaperone by guiding nucleic-acid sensing toll-like receptors (TLRs) to their respective endosomal signaling compartments. We previously showed that UNC93B1 interacts with STIM1 to promote antigen cross-presentation in dendritic cells, but the STIM1 binding site(s) and activation step(s) impacted by this interaction remained unknown. In this study, we show that UNC93B1 interacts with STIM1 in the ER lumen by binding to residues in close proximity to the transmembrane domain. Cysteine cross-linking in-vivo showed that UNC93B1 binding promotes the zipping of transmembrane and proximal cytosolic helices within resting STIM1 dimers, priming STIM1 for translocation. In addition, we show that UNC93B1 deficiency reduces SOCE and STIM1/Orai1 interactions and targets STIM1 to lighter ER domains, while UNC93B1 expression accelerates the recruitment of STIM1 to cortical ER domains. We conclude that UNC93B1 therefore acts as a trafficking chaperone by maintaining the pool of resting STIM1 proteins in a state primed for activation, enabling their rapid translocation in an extended conformation to cortical ER signaling compartments.

Keywords: calcium signaling; innate immunity; ion channels; membrane contact sites; protein trafficking

DOI: https://doi.org/10.1016/j.jbc.2022.101607