-
Molecular Cell Apr 2022Organelles are continuously turned over as part of cellular homeostasis and adaptation. Most organelles, even including the nucleus, are degraded by lysosomes via...
Organelles are continuously turned over as part of cellular homeostasis and adaptation. Most organelles, even including the nucleus, are degraded by lysosomes via different pathways, such as macroautophagy, microautophagy, organelle-derived vesicle degradation, and crinophagy. In some specific cases-for example, in lens fiber cells-organelles are degraded by cytosolic phospholipases. To view this SnapShot, open or download the PDF.
Topics: Autophagy; Cytosol; Lens, Crystalline; Lysosomes; Organelles
PubMed: 35452619
DOI: 10.1016/j.molcel.2022.03.015 -
MBio Aug 2021Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites... (Review)
Review
Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites replicate through endodyogeny, during which two daughter cells are formed within the parental cell, P. falciparum replicates through schizogony, where up to 32 parasites are formed in a single infected red blood cell and even thousands of daughter cells during mosquito- or liver-stage development. These processes require a tightly orchestrated division and distribution over the daughter parasites of one-per-cell organelles such as the mitochondrion and apicoplast. Although proper organelle segregation is highly essential, the molecular mechanism and the key proteins involved remain largely unknown. In this review, we describe organelle dynamics during cell division in T. gondii and P. falciparum, summarize the current understanding of the molecular mechanisms underlying organelle fission in these parasites, and introduce candidate fission proteins.
Topics: Animals; Apicoplasts; Erythrocytes; Humans; Mitochondria; Parasites; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 34425697
DOI: 10.1128/mBio.01409-21 -
Cells Sep 2022Liquid-liquid phase separation (LLPS) is a biochemical process in cells that can drive proteins, RNA, and other molecules to concentrate into droplets. These droplets do... (Review)
Review
Liquid-liquid phase separation (LLPS) is a biochemical process in cells that can drive proteins, RNA, and other molecules to concentrate into droplets. These droplets do not have a lipid membrane but rather exist as distinct organelles relative to the surrounding environment, and act as biochemical reaction chambers. In recent years, significant progress has been made in the study of LLPS, especially in the neurodegenerative disease, cancer, and virology fields, but little is known about LLPS in cardiovascular disease (CVD). In this review, we discuss the current understanding of the mechanism and biological functions of LLPS, particularly its roles in regulating CVD.
Topics: Cardiovascular Diseases; Humans; Lipids; Neurodegenerative Diseases; Organelles; RNA
PubMed: 36231002
DOI: 10.3390/cells11193040 -
Current Opinion in Cell Biology Apr 2022The majority of the proteome in eukaryotic cells is targeted to organelles. To maintain protein homeostasis (proteostasis), distinct protein quality control (PQC)... (Review)
Review
The majority of the proteome in eukaryotic cells is targeted to organelles. To maintain protein homeostasis (proteostasis), distinct protein quality control (PQC) machineries operate on organelles, where they detect misfolded proteins, orphaned and mis-localized proteins and selectively target these proteins into different ubiquitin-dependent or -independent degradation pathways. Thereby, PQC prevents proteotoxic effects that would disrupt organelle integrity and cause cellular damage that leads to diseases. Here, we will discuss emerging mechanisms for PQC machineries at the Golgi apparatus, the central station for the sorting and the modification of proteins that traffic to the endo-lysosomal system, or along the secretory pathway to the PM and to the extracellular space. We will focus on Golgi PQC pathways that (1) retrieve misfolded and orphaned proteins from the Golgi back to the endoplasmic reticulum, (2) extract these proteins from Golgi membranes for proteasomal degradation, (3) or selectively target these proteins to lysosomes for degradation.
Topics: Endoplasmic Reticulum; Golgi Apparatus; Protein Transport; Proteins; Proteostasis; Ubiquitin
PubMed: 35364487
DOI: 10.1016/j.ceb.2022.02.008 -
Biological Chemistry May 2020Mitochondria are surrounded by the two membranes, the outer and inner membranes, whose lipid compositions are optimized for proper functions and structural organizations... (Review)
Review
Mitochondria are surrounded by the two membranes, the outer and inner membranes, whose lipid compositions are optimized for proper functions and structural organizations of mitochondria. Although a part of mitochondrial lipids including their characteristic lipids, phosphatidylethanolamine and cardiolipin, are synthesized within mitochondria, their precursor lipids and other lipids are transported from other organelles, mainly the ER. Mitochondrially synthesized lipids are re-distributed within mitochondria and to other organelles, as well. Recent studies pointed to the important roles of inter-organelle contact sites in lipid trafficking between different organelle membranes. Identification of Ups/PRELI proteins as lipid transfer proteins shuttling between the mitochondrial outer and inner membranes established a part of the molecular and structural basis of the still elusive intra-mitochondrial lipid trafficking.
Topics: Carrier Proteins; Homeostasis; Lipid Metabolism; Mitochondria; Phospholipids
PubMed: 32229651
DOI: 10.1515/hsz-2020-0121 -
Cells Sep 2022The Golgi apparatus (GA) is essential for intracellular sorting, trafficking and the targeting of proteins to specific cellular compartments. Anatomically, the GA... (Review)
Review
The Golgi apparatus (GA) is essential for intracellular sorting, trafficking and the targeting of proteins to specific cellular compartments. Anatomically, the GA spreads all over the cell but is also particularly enriched close to the base of the primary cilium. This peculiar organelle protrudes at the surface of almost all cells and fulfills many cellular functions, in particular during development, when a dysfunction of the primary cilium can lead to disorders called ciliopathies. While ciliopathies caused by loss of ciliated proteins have been extensively documented, several studies suggest that alterations of GA and GA-associated proteins can also affect ciliogenesis. Here, we aim to discuss how the loss-of-function of genes coding these proteins induces ciliary defects and results in ciliopathies.
Topics: Cell Movement; Cilia; Ciliopathies; Golgi Apparatus; Humans; Organelles
PubMed: 36139347
DOI: 10.3390/cells11182773 -
Genes & Development Apr 2021Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of... (Review)
Review
Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. This review aims to present novel findings on the cellular interorganelle communication network and how its dysfunction may contribute to aging and neurodegeneration. The consequences of disturbed interorganellar communication are intimately linked with age-related pathologies. Given that both aging and neurodegenerative diseases are characterized by the concomitant failure of multiple cellular pathways, coordination of organelle communication and function could represent an emerging regulatory mechanism critical for long-term cellular homeostasis. We anticipate that defining the relationships between interorganelle communication, aging, and neurodegeneration will open new avenues for therapeutics.
Topics: Animals; Cellular Senescence; Humans; Neurodegenerative Diseases; Organelles; Signal Transduction
PubMed: 33861720
DOI: 10.1101/gad.346759.120 -
Traffic (Copenhagen, Denmark) Nov 2020This review considers the following hypotheses, some well-supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with... (Review)
Review
This review considers the following hypotheses, some well-supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter-organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins-receptors, channels and transporters-at least in vitro.
Topics: Caveolae; Cell Membrane; Cholesterol; Phospholipids; Sterols
PubMed: 32930466
DOI: 10.1111/tra.12762 -
Journal of Bacteriology Mar 2022Increasing efficiency is an important driving force behind cellular organization and often achieved through compartmentalization. Long recognized as a core principle of... (Review)
Review
Increasing efficiency is an important driving force behind cellular organization and often achieved through compartmentalization. Long recognized as a core principle of eukaryotic cell organization, its widespread occurrence in prokaryotes has only recently come to light. Despite the early discovery of a few microcompartments, such as gas vesicles and carboxysomes, the vast majority of these structures in prokaryotes are less than 100 nm in diameter-too small for conventional light microscopy and electron microscopic thin sectioning. Consequently, these smaller nanocompartments have been discovered serendipitously and then through bioinformatics shown to be broadly distributed. Their small uniform size, robust self-assembly, high stability, excellent biocompatibility, and large cargo capacity make them excellent candidates for biotechnology applications. This review will highlight our current knowledge of nanocompartments and the prospects for applications, as well as open questions and challenges that need to be addressed to fully understand these important structures.
Topics: Bacteria; Bacterial Proteins; Organelles
PubMed: 34606372
DOI: 10.1128/JB.00346-21 -
Biochemical Society Transactions Oct 2022Advances in public health have nearly doubled life expectancy over the last century, but this demographic shift has also changed the landscape of human illness. Today,... (Review)
Review
Advances in public health have nearly doubled life expectancy over the last century, but this demographic shift has also changed the landscape of human illness. Today, chronic and age-dependent diseases dominate the leading causes of morbidity and mortality worldwide. Targeting the underlying molecular, genetic and cell biological drivers of the aging process itself appears to be an increasingly viable strategy for developing therapeutics against these diseases of aging. Towards this end, one of the most exciting developments in cell biology over the last decade is the explosion of research into organelle contact sites and related mechanisms of inter-organelle communication. Identification of the molecular mediators of inter-organelle tethering and signaling is now allowing the field to investigate the consequences of aberrant organelle interactions, which frequently seem to correlate with age-onset pathophysiology. This review introduces the major cellular roles for inter-organelle interactions, including the regulation of organelle morphology, the transfer of ions, lipids and other metabolites, and the formation of hubs for nutrient and stress signaling. We explore how these interactions are disrupted in aging and present findings that modulation of inter-organelle communication is a promising avenue for promoting longevity. Through this review, we propose that the maintenance of inter-organelle interactions is a pillar of healthy aging. Learning how to target the cellular mechanisms for sensing and controlling inter-organelle communication is a key next hurdle for geroscience.
Topics: Humans; Aging; Longevity; Mitochondrial Membranes; Organelles; Cell Communication
PubMed: 36305642
DOI: 10.1042/BST20220519