Review

Authors: Shunbang Yu, Li Yu

The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate-like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.

Topics: Cell Movement; Organelles; Mitochondria; Signal Transduction; Organelle Biogenesis

PubMed: 34492154
DOI: 10.1111/febs.16183

Review

Authors: Edward Gomes, James Shorter

Eukaryotic cells organize their intracellular components into organelles that can be membrane-bound or membraneless. A large number of membraneless organelles, including nucleoli, Cajal bodies, P-bodies, and stress granules, exist as liquid droplets within the cell and arise from the condensation of cellular material in a process termed liquid-liquid phase separation (LLPS). Beyond a mere organizational tool, concentrating cellular components into membraneless organelles tunes biochemical reactions and improves cellular fitness during stress. In this review, we provide an overview of the molecular underpinnings of the formation and regulation of these membraneless organelles. This molecular understanding explains emergent properties of these membraneless organelles and shines new light on neurodegenerative diseases, which may originate from disturbances in LLPS and membraneless organelles.

Topics: Cell Physiological Phenomena; Cytoplasm; Humans; Organelles

PubMed: 30045872
DOI: 10.1074/jbc.TM118.001192

Review

Authors: Xuebing Xu, Tong Wu, Renjie Lin...

The migrasome is a new organelle discovered by Professor Yu Li in 2015. When cells migrate, the membranous organelles that appear at the end of the retraction fibres are migrasomes. With the migration of cells, the retraction fibres which connect migrasomes and cells finally break. The migrasomes detach from the cell and are released into the extracellular space or directly absorbed by the recipient cell. The cytoplasmic contents are first transported to the migrasome and then released from the cell through the migrasome. This release mechanism, which depends on cell migration, is named 'migracytosis'. The main components of the migrasome are extracellular vesicles after they leave the cell, which are easy to remind people of the current hot topic of exosomes. Exosomes are extracellular vesicles wrapped by the lipid bimolecular layer. With extensive research, exosomes have solved many disease problems. This review summarizes the differences between migrasomes and exosomes in size, composition, property and function, extraction method and regulation mechanism for generation and release. At the same time, it also prospects for the current hotspot of migrasomes, hoping to provide literature support for further research on the generation and release mechanism of migrasomes and their clinical application in the future.

Topics: Humans; Exosomes; Organelles; Cell Movement; Extracellular Vesicles; Biological Transport

PubMed: 37665060
DOI: 10.1111/jcmm.17942

Review

Authors: Haoxi Wu, Pedro Carvalho, Gia K Voeltz...

Our textbook image of organelles has changed. Instead of revealing isolated cellular compartments, the picture now emerging shows organelles as largely interdependent structures that can communicate through membrane contact sites (MCSs). MCSs are sites where opposing organelles are tethered but do not fuse. MCSs provide a hybrid location where the tool kits of two different organelles can work together to perform vital cellular functions, such as lipid and ion transfer, signaling, and organelle division. Here, we focus on MCSs involving the endoplasmic reticulum (ER), an organelle forming an extensive network of cisternae and tubules. We highlight how the dynamic ER network regulates a plethora of cellular processes through MCSs with various organelles and with the plasma membrane.

Topics: Animals; Calcium; Cell Membrane; Endoplasmic Reticulum; Endosomes; Humans; Lipid Droplets; Lipid Metabolism; Metabolic Networks and Pathways; Microscopy, Fluorescence; Mitochondria; Neurodegenerative Diseases; Peroxisomes; Vesicular Transport Proteins

PubMed: 30072511
DOI: 10.1126/science.aan5835

Review

Authors: Jonathan R Friedman, Jodi Nunnari

Mitochondria are one of the major ancient endomembrane systems in eukaryotic cells. Owing to their ability to produce ATP through respiration, they became a driving force in evolution. As an essential step in the process of eukaryotic evolution, the size of the mitochondrial chromosome was drastically reduced, and the behaviour of mitochondria within eukaryotic cells radically changed. Recent advances have revealed how the organelle's behaviour has evolved to allow the accurate transmission of its genome and to become responsive to the needs of the cell and its own dysfunction.

Topics: Animals; Chromosome Segregation; Chromosomes; DNA, Mitochondrial; Dynamins; Endoplasmic Reticulum; Eukaryotic Cells; Genome, Mitochondrial; Humans; Mitochondria; Organelle Shape; Stress, Physiological

PubMed: 24429632
DOI: 10.1038/nature12985

Review

Authors: Meiqin Hu, Xinghua Feng, Qiang Liu...

The endomembrane system consists of organellar membranes in the biosynthetic pathway [endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles] as well as those in the degradative pathway (early endosomes, macropinosomes, phagosomes, autophagosomes, late endosomes, and lysosomes). These endomembrane organelles/vesicles work together to synthesize, modify, package, transport, and degrade proteins, carbohydrates, and lipids, regulating the balance between cellular anabolism and catabolism. Large ion concentration gradients exist across endomembranes: Ca gradients for most endomembrane organelles and H gradients for the acidic compartments. Ion (Na, K, H, Ca, and Cl) channels on the organellar membranes control ion flux in response to cellular cues, allowing rapid informational exchange between the cytosol and organelle lumen. Recent advances in organelle proteomics, organellar electrophysiology, and luminal and juxtaorganellar ion imaging have led to molecular identification and functional characterization of about two dozen endomembrane ion channels. For example, whereas IP3R1-3 channels mediate Ca release from the ER in response to neurotransmitter and hormone stimulation, TRPML1-3 and TMEM175 channels mediate lysosomal Ca and H release, respectively, in response to nutritional and trafficking cues. This review aims to summarize the current understanding of these endomembrane channels, with a focus on their subcellular localizations, ion permeation properties, gating mechanisms, cell biological functions, and disease relevance.

Topics: Humans; Animals; Ion Channels; Intracellular Membranes; Organelles

PubMed: 38451235
DOI: 10.1152/physrev.00025.2023

Review

Authors: Eva Jarc, Toni Petan

Lipid droplets are cytosolic fat storage organelles present in most eukaryotic cells. Long regarded merely as inert fat reservoirs, they are now emerging as major regulators of cellular metabolism. They act as hubs that coordinate the pathways of lipid uptake, distribution, storage, and use in the cell. Recent studies have revealed that they are also essential components of the cellular stress response. One of the hallmark characteristics of lipid droplets is their capacity to buffer excess lipids and to finely tune their subsequent release based on specific cellular requirements. This simple feature of lipid droplet biology, buffering and delayed release of lipids, forms the basis for their pleiotropic roles in the cellular stress response. In stressed cells, lipid droplets maintain energy and redox homeostasis and protect against lipotoxicity by sequestering toxic lipids into their neutral lipid core. Their mobility and dynamic interactions with mitochondria enable an efficient delivery of fatty acids for optimal energy production. Lipid droplets are also involved in the maintenance of membrane and organelle homeostasis by regulating membrane composition, preventing lipid peroxidation and removing damaged proteins and lipids. Finally, they also engage in a symbiotic relationship with autophagy and act as reservoirs of bioactive lipids that regulate inflammation and immunity. Thus, lipid droplets are central managers of lipid metabolism that function as safeguards against various types of cellular stress.

Topics: Animals; Energy Metabolism; Homeostasis; Humans; Lipid Droplets; Lipids; Organelles; Stress, Physiological

PubMed: 31543707
DOI: No ID Found

Review

Authors: Sarah Cohen, Alex M Valm, Jennifer Lippincott-Schwartz...

Eukaryotic cells are organized into membrane-bound organelles. These organelles communicate with one another through vesicular trafficking pathways and membrane contact sites (MCSs). MCSs are sites of close apposition between two or more organelles that play diverse roles in the exchange of metabolites, lipids and proteins. Organelle interactions at MCSs also are important for organelle division and biogenesis. For example, the division of several organelles, including mitochondria and endosomes, seem to be regulated by contacts with the endoplasmic reticulum (ER). Moreover, the biogenesis of autophagosomes and peroxisomes involves contributions from the ER and multiple other cellular compartments. Thus, organelle-organelle interactions allow cells to alter the shape and activities of their membrane-bound compartments, allowing them to cope with different developmental and environmental conditions.

Topics: Animals; Eukaryotic Cells; Humans; Intracellular Membranes; Organelles; Protein Transport

PubMed: 30006038
DOI: 10.1016/j.ceb.2018.06.003

Authors: Liang Ma, Ying Li, Junya Peng...

Cells communicate with each other through secreting and releasing proteins and vesicles. Many cells can migrate. In this study, we report the discovery of migracytosis, a cell migration-dependent mechanism for releasing cellular contents, and migrasomes, the vesicular structures that mediate migracytosis. As migrating cells move, they leave long tubular strands, called retraction fibers, behind them. Large vesicles, which contain numerous smaller vesicles, grow on the tips and intersections of retraction fibers. These fibers, which connect the vesicles with the main cell body, eventually break, and the vesicles are released into the extracellular space or directly taken up by surrounding cells. Since the formation of these vesicles is migration-dependent, we named them "migrasomes". We also found that cytosolic contents can be transported into migrasomes and released from the cell through migrasomes. We named this migration-dependent release mechanism "migracytosis".

Topics: Actins; Animals; Biological Transport; Cell Line; Cell Line, Tumor; Cell Movement; Cytoplasm; Humans; Mice; Organelles

PubMed: 25342562
DOI: 10.1038/cr.2014.135

Authors: Julia A Zimmermann, Kerstin Lucht, Manuel Stecher...

Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multi-spectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (mitochondria-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (mitochondria-ER-peroxisome-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid mediator synthesis. Together, we show that macrophages form functional multi-organellar units to support metabolic adaptation and provide an experimental strategy to identify organelle-metabolic signalling hubs.

Topics: Macrophages; Lipid Metabolism; Animals; Endoplasmic Reticulum; Lipid Droplets; Mitochondria; Inflammation; Fatty Acids; Peroxisomes; Mice; Mice, Inbred C57BL; Signal Transduction; Organelles

PubMed: 38969763
DOI: 10.1038/s41556-024-01457-0