bims-mecosi 2022-12-18 papers

bims-mecosi

Biomed News

on Membrane contact sites

Issue of 2022–12–18
eight papers selected by
Verena Kohler, University of Graz

Membrane Contact Sites in Autophagy.
CARTS Formation Assay.
Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction.
Editorial: Cell compartments and intracellular trafficking of lipids and proteins: Impact on biomedicine.
Super-Resolution Microscopy to Study Interorganelle Contact Sites.
Molecular insights into endolysosomal microcompartment formation and maintenance.
Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function.
Lysosome signaling in cell survival and programmed cell death for cellular homeostasis.

Cells. 2022 Nov 28. pii: 3813. [Epub ahead of print]11(23):

Membrane Contact Sites in Autophagy.

Emma Zwilling, Fulvio Reggiori.

  Eukaryotes utilize different communication strategies to coordinate processes between different cellular compartments either indirectly, through vesicular transport, or directly, via membrane contact sites (MCSs). MCSs have been implicated in lipid metabolism, calcium signaling and the regulation of organelle biogenesis in various cell types. Several studies have shown that MCSs play a crucial role in the regulation of macroautophagy, an intracellular catabolic transport route that is characterized by the delivery of cargoes (proteins, protein complexes or aggregates, organelles and pathogens) to yeast and plant vacuoles or mammalian lysosomes, for their degradation and recycling into basic metabolites. Macroautophagy is characterized by the de novo formation of double-membrane vesicles called autophagosomes, and their biogenesis requires an enormous amount of lipids. MCSs appear to have a central role in this supply, as well as in the organization of the autophagy-related (ATG) machinery. In this review, we will summarize the evidence for the participation of specific MCSs in autophagosome formation, with a focus on the budding yeast and mammalian systems.

Keywords:  MAMs; autophagosome; endoplasmic reticulum; lipid droplets; lipid transfer; mitochondria; phagophore; plasma membrane; vacuole

DOI:  https://doi.org/10.3390/cells11233813
Methods Mol Biol. 2023 ;2557 573-581

CARTS Formation Assay.

Yuichi Wakana, Mitsuo Tagaya.

  Sorting and transport of secretory and membrane proteins occur at the trans-Golgi network (TGN). Carriers of the TGN to the cell surface (CARTS) are one of the carriers that mediate the transport of certain proteins from the TGN to the plasma membrane. Recent studies have shown that CARTS formation is dependent on membrane contact sites between the Golgi apparatus and the endoplasmic reticulum (ER). Here, we describe a method to visualize by fluorescence microscopy the formation of CARTS at the TGN. This method combines a reverse dimerization system for synchronized export from the ER of a CARTS-specific cargo, pancreatic adenocarcinoma upregulated factor, together with the halt of export from the TGN by a 20 °C block. Incubation of cells at 37 °C releases the 20 °C block and allows to monitor the formation of CARTS at the TGN. Finally, we also present a workflow to quantify CARTS formation using ImageJ software.

Keywords:  Membrane contact sites; Membrane trafficking; Protein kinase D; Reverse dimerization system; Trans-Golgi network

DOI:  https://doi.org/10.1007/978-1-0716-2639-9_34
Front Cell Dev Biol. 2022 ;10 1036225

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction.

Tao Jiang, Qian Wang, Jiagao Lv, Li Lin.

  Mitochondrial and endoplasmic reticulum (ER) are important intracellular organelles. The sites that mitochondrial and ER are closely related in structure and function are called Mitochondria-ER contacts (MERCs). MERCs are involved in a variety of biological processes, including calcium signaling, lipid synthesis and transport, autophagy, mitochondrial dynamics, ER stress, and inflammation. Sepsis-induced myocardial dysfunction (SIMD) is a vital organ damage caused by sepsis, which is closely associated with mitochondrial and ER dysfunction. Growing evidence strongly supports the role of MERCs in the pathogenesis of SIMD. In this review, we summarize the biological functions of MERCs and the roles of MERCs proteins in SIMD.

Keywords:  ER stress; autophagy; calcium signaling; inflammation; mitochondria-ER contacts; mitochondrial dynamics; sepsis-induced myocardial dysfunction

DOI:  https://doi.org/10.3389/fcell.2022.1036225
Front Cell Dev Biol. 2022 ;10 1087214

Editorial: Cell compartments and intracellular trafficking of lipids and proteins: Impact on biomedicine.

Silvana Zanlungo, Carlos Enrich, Volker Gerke, Emily R Eden, María Isabel Colombo.



Keywords:  Endosomes; cholesterol; disease models; lipid droplets; lysosomal storage diseases; lysosome-related organelles; lysosomes; membrane contact sites

DOI:  https://doi.org/10.3389/fcell.2022.1087214
Int J Mol Sci. 2022 Dec 05. pii: 15354. [Epub ahead of print]23(23):

Super-Resolution Microscopy to Study Interorganelle Contact Sites.

Jon Ander Nieto-Garai, June Olazar-Intxausti, Itxaso Anso, Maier Lorizate, Oihana Terrones, Francesc-Xabier Contreras.

  Interorganelle membrane contact sites (MCS) are areas of close vicinity between the membranes of two organelles that are maintained by protein tethers. Recently, a significant research effort has been made to study MCS, as they are implicated in a wide range of biological functions, such as organelle biogenesis and division, apoptosis, autophagy, and ion and phospholipid homeostasis. Their composition, characteristics, and dynamics can be studied by different techniques, but in recent years super-resolution fluorescence microscopy (SRFM) has emerged as a powerful tool for studying MCS. In this review, we first explore the main characteristics and biological functions of MCS and summarize the different approaches for studying them. Then, we center on SRFM techniques that have been used to study MCS. For each of the approaches, we summarize their working principle, discuss their advantages and limitations, and explore the main discoveries they have uncovered in the field of MCS.

Keywords:  PALM; SIM; SMLM; STED; STORM; TIRFM; membrane contact sites; organelles; super-resolution microscopy

DOI:  https://doi.org/10.3390/ijms232315354
Biol Chem. 2022 Dec 13.

Molecular insights into endolysosomal microcompartment formation and maintenance.

Daniel Kümmel, Eric Herrmann, Lars Langemeyer, Christian Ungermann.

  The endolysosomal system of eukaryotic cells has a key role in the homeostasis of the plasma membrane, in signaling and nutrient uptake, and is abused by viruses and pathogens for entry. Endocytosis of plasma membrane proteins results in vesicles, which fuse with the early endosome. If destined for lysosomal degradation, these proteins are packaged into intraluminal vesicles, converting an early endosome to a late endosome, which finally fuses with the lysosome. Each of these organelles has a unique membrane surface composition, which can form segmented membrane microcompartments by membrane contact sites or fission proteins. Furthermore, these organelles are in continuous exchange due to fission and fusion events. The underlying machinery, which maintains organelle identity along the pathway, is regulated by signaling processes. Here, we will focus on the Rab5 and Rab7 GTPases of early and late endosomes. As molecular switches, Rabs depend on activating guanine nucleotide exchange factors (GEFs). Over the last years, we characterized the Rab7 GEF, the Mon1-Ccz1 (MC1) complex, and key Rab7 effectors, the HOPS complex and retromer. Structural and functional analyses of these complexes lead to a molecular understanding of their function in the context of organelle biogenesis.

Keywords:  GEF; HOPS; endosome; lysosome; membrane fusion; tethering

DOI:  https://doi.org/10.1515/hsz-2022-0294
Science. 2022 Dec 16. 378(6625): eabq5209

Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function.

Wonyul Jang, Dmytro Puchkov, Paula Samsó, YongTian Liang, Michal Nadler-Holly, Stephan J Sigrist, Ulrich Kintscher, Fan Liu, Kamel Mamchaoui, Vincent Mouly, Volker Haucke.

Cells respond to fluctuating nutrient supply by adaptive changes in organelle dynamics and in metabolism. How such changes are orchestrated on a cell-wide scale is unknown. We show that endosomal signaling lipid turnover by MTM1, a phosphatidylinositol 3-phosphate [PI(3)P] 3-phosphatase mutated in X-linked centronuclear myopathy in humans, controls mitochondrial morphology and function by reshaping the endoplasmic reticulum (ER). Starvation-induced endosomal recruitment of MTM1 impairs PI(3)P-dependent contact formation between tubular ER membranes and early endosomes, resulting in the conversion of ER tubules into sheets, the inhibition of mitochondrial fission, and sustained oxidative metabolism. Our results unravel an important role for early endosomal lipid signaling in controlling ER shape and, thereby, mitochondrial form and function to enable cells to adapt to fluctuating nutrient environments.

DOI: https://doi.org/10.1126/science.abq5209
J Cell Physiol. 2022 Dec 11.

Lysosome signaling in cell survival and programmed cell death for cellular homeostasis.

Srimanta Patra, Shankargouda Patil, Daniel J Klionsky, Sujit K Bhutia.

  Recent developments in lysosome biology have transformed our view of lysosomes from static garbage disposals that can also act as suicide bags to decidedly dynamic multirole adaptive operators of cellular homeostasis. Lysosome-governed signaling pathways, proteins, and transcription factors equilibrate the rate of catabolism and anabolism (autophagy to lysosomal biogenesis and metabolite pool maintenance) by sensing cellular metabolic status. Lysosomes also interact with other organelles by establishing contact sites through which they exchange cellular contents. Lysosomal function is critically assessed by lysosomal positioning and motility for cellular adaptation. In this setting, mechanistic target of rapamycin kinase (MTOR) is the chief architect of lysosomal signaling to control cellular homeostasis. Notably, lysosomes can orchestrate explicit cell death mechanisms, such as autophagic cell death and lysosomal membrane permeabilization-associated regulated necrotic cell death, to maintain cellular homeostasis. These lines of evidence emphasize that the lysosomes serve as a central signaling hub for cellular homeostasis.

Keywords:  autophagy; lysosomal biogenesis; lysosomal membrane permeabilization; lysosome; mechanistic target of rapamycin kinase

DOI:  https://doi.org/10.1002/jcp.30928