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Cell Reports Oct 2023Dysfunctional mitochondria are removed via multiple pathways, such as mitophagy, a selective autophagy process. Here, we identify an intracellular hybrid...
Dysfunctional mitochondria are removed via multiple pathways, such as mitophagy, a selective autophagy process. Here, we identify an intracellular hybrid mitochondria-lysosome organelle (termed the mitochondria-lysosome-related organelle [MLRO]), which regulates mitochondrial homeostasis independent of canonical mitophagy during hepatocyte dedifferentiation. The MLRO is an electron-dense organelle that has either a single or double membrane with both mitochondria and lysosome markers. Mechanistically, the MLRO is likely formed from the fusion of mitochondria-derived vesicles (MDVs) with lysosomes through a PARKIN-, ATG5-, and DRP1-independent process, which is negatively regulated by transcription factor EB (TFEB) and associated with mitochondrial protein degradation and hepatocyte dedifferentiation. The MLRO, which is galectin-3 positive, is reminiscent of damaged lysosome and could be cleared by overexpression of TFEB, resulting in attenuation of hepatocyte dedifferentiation. Together, results from this study suggest that the MLRO may act as an alternative mechanism for mitochondrial quality control independent of canonical autophagy/mitophagy involved in cell dedifferentiation.
Topics: Mitochondria; Organelles; Lysosomes; Autophagy; Mitophagy
PubMed: 37862166
DOI: 10.1016/j.celrep.2023.113291 -
The EMBO Journal Jul 2023Chloroplasts are plant organelles responsible for photosynthesis and environmental sensing. Most chloroplast proteins are imported from the cytosol through the...
Chloroplasts are plant organelles responsible for photosynthesis and environmental sensing. Most chloroplast proteins are imported from the cytosol through the translocon at the outer envelope membrane of chloroplasts (TOC). Previous work has shown that TOC components are regulated by the ubiquitin-proteasome system (UPS) to control the chloroplast proteome, which is crucial for the organelle's function and plant development. Here, we demonstrate that the TOC apparatus is also subject to K63-linked polyubiquitination and regulation by selective autophagy, potentially promoting plant stress tolerance. We identify NBR1 as a selective autophagy adaptor targeting TOC components, and mediating their relocation into vacuoles for autophagic degradation. Such selective autophagy is shown to control TOC protein levels and chloroplast protein import and to influence photosynthetic activity as well as tolerance to UV-B irradiation and heat stress in Arabidopsis plants. These findings uncover the vital role of selective autophagy in the proteolytic regulation of specific chloroplast proteins, and how dynamic control of chloroplast protein import is critically important for plants to cope with challenging environments.
Topics: Chloroplasts; Plants; Organelles; Protein Transport; Chloroplast Proteins; Arabidopsis; Autophagy; Plant Proteins; Arabidopsis Proteins; Carrier Proteins
PubMed: 37248861
DOI: 10.15252/embj.2022112534 -
Nature Sep 2019The ability of proteins and nucleic acids to undergo liquid-liquid phase separation has recently emerged as an important molecular principle of how cells rapidly and...
The ability of proteins and nucleic acids to undergo liquid-liquid phase separation has recently emerged as an important molecular principle of how cells rapidly and reversibly compartmentalize their components into membrane-less organelles such as the nucleolus, processing bodies or stress granules. How the assembly and turnover of these organelles are controlled, and how these biological condensates selectively recruit or release components are poorly understood. Here we show that members of the large and highly abundant family of RNA-dependent DEAD-box ATPases (DDXs) are regulators of RNA-containing phase-separated organelles in prokaryotes and eukaryotes. Using in vitro reconstitution and in vivo experiments, we demonstrate that DDXs promote phase separation in their ATP-bound form, whereas ATP hydrolysis induces compartment turnover and release of RNA. This mechanism of membrane-less organelle regulation reveals a principle of cellular organization that is conserved from bacteria to humans. Furthermore, we show that DDXs control RNA flux into and out of phase-separated organelles, and thus propose that a cellular network of dynamic, DDX-controlled compartments establishes biochemical reaction centres that provide cells with spatial and temporal control of various RNA-processing steps, which could regulate the composition and fate of ribonucleoprotein particles.
Topics: Adenosine Triphosphatases; Biocatalysis; Cell Compartmentation; Cell Line; Conserved Sequence; Cytoplasmic Granules; DEAD-box RNA Helicases; Eukaryotic Cells; Evolution, Molecular; Humans; Organelles; Prokaryotic Cells; RNA; RNA Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 31435012
DOI: 10.1038/s41586-019-1502-y -
Cold Spring Harbor Perspectives in... Oct 2023The sorting and trafficking of lipids between organelles gives rise to a dichotomy of bulk membrane properties between organelles of the secretory and endolysosome... (Review)
Review
The sorting and trafficking of lipids between organelles gives rise to a dichotomy of bulk membrane properties between organelles of the secretory and endolysosome networks, giving rise to two "membrane territories" based on differences in lipid-packing density, net membrane charge, and bilayer leaflet asymmetries. The cellular organelle membrane dichotomy emerges from ER-to-PM anterograde membrane trafficking and the synthesis of sphingolipids and cholesterol flux at the -Golgi network, which constitutes the interface between the two membrane territories. Organelle homeostasis is maintained by vesicle-mediated retrieval of bulk membrane from the distal organelles of each territory to the endoplasmic reticulum or plasma membrane and by soluble lipid transfer proteins that traffic particular lipids. The concept of cellular membrane territories emphasizes the contrasting features of organelle membranes of the secretory and endolysosome networks and the essential roles of lipid-sorting pathways that maintain organelle function.
Topics: Endoplasmic Reticulum; Cell Membrane; Protein Transport; Biological Transport; Lipids
PubMed: 37487627
DOI: 10.1101/cshperspect.a041397 -
Science (New York, N.Y.) Apr 2024A bacterial endosymbiont of marine algae evolved to an organelle.
A bacterial endosymbiont of marine algae evolved to an organelle.
Topics: Nitrogen; Organelles; Bacteria
PubMed: 38603513
DOI: 10.1126/science.ado8571 -
Cell Structure and Function Aug 2019In research on cell biology, organelles have been a major unit of such analyses. Researchers have assumed that the inside of an organelle is almost uniform in regards to... (Review)
Review
In research on cell biology, organelles have been a major unit of such analyses. Researchers have assumed that the inside of an organelle is almost uniform in regards to its function, even though each organelle has multiple functions. However, we are now facing conundrums that cannot be resolved so long as we regard organelles as functionally uniform units. For instance, how can cells control the diverse patterns of glycosylation of various secretory proteins in the endoplasmic reticulum and Golgi in an orderly manner with high accuracy? Here, we introduce the novel concept of organelle zones as a solution; each organelle has functionally distinct zones, and zones in different organelles closely interact each other in order to perform complex cellular functions. This Copernican Revolution from organelle biology to organelle zone biology will drastically change and advance our thoughts about cells.Key words: organelle zone, contact site, ER stress, Golgi stress, organelle autoregulation.
Topics: Animals; Endoplasmic Reticulum; Golgi Apparatus; Humans; Organelles
PubMed: 31308351
DOI: 10.1247/csf.19010 -
Chemical Communications (Cambridge,... Sep 2020Radiotherapy (RT) has been extensively applied in clinical cancer therapy. However, cancer cells usually exhibit high resistance to radiation, ultimately resulting in... (Review)
Review
Radiotherapy (RT) has been extensively applied in clinical cancer therapy. However, cancer cells usually exhibit high resistance to radiation, ultimately resulting in the failure of tumor eradication. Recently, a series of radiosensitizers that can selectively accumulate into specific organelles inside cancer cells have been developed, providing new opportunities for overcoming radioresistance and boosting radiosensitivity. In this Review, the progress and future directions of organelle-targeted radiosensitizers will be introduced, which aims to offer valuable information toward better-designed radiosensitizers for clinical cancer therapy.
Topics: Animals; Cell Line, Tumor; Cell Membrane; Humans; Mitochondria; Neoplasms; Organelles; Radiation-Sensitizing Agents
PubMed: 32930179
DOI: 10.1039/d0cc03245j -
Biochemical Society Transactions Feb 2021Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that... (Review)
Review
Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that regulate glycosomes are conserved, there are several unique aspects of their biology that are divergent from other systems and may be leveraged as therapeutic targets for the treatment of kinetoplastid diseases. Glycosomes are heterogeneous organelles that likely exist as sub-populations with different protein composition and function in a given cell, between individual cells, and between species. However, the limitations posed by the small size of these organelles makes the study of this heterogeneity difficult. Recent advances in the analysis of small vesicles by flow-cytometry provide an opportunity to overcome these limitations. In this review, we describe studies that document the diverse nature of glycosomes and propose an approach to using flow cytometry and organelle sorting to study the diverse composition and function of these organelles. Because the cellular machinery that regulates glycosome protein import and biogenesis is likely to contribute, at least in part, to glycosome heterogeneity we highlight some ways in which the glycosome protein import machinery differs from that of peroxisomes in other eukaryotes.
Topics: Animals; Kinetoplastida; Microbodies; Peroxisomes; Protein Transport; Protozoan Proteins
PubMed: 33439256
DOI: 10.1042/BST20190517 -
Molecular Cell Mar 2023Mitochondria are membrane-enclosed organelles with endosymbiotic origins, harboring independent genomes and a unique biochemical reaction network. To perform their... (Review)
Review
Mitochondria are membrane-enclosed organelles with endosymbiotic origins, harboring independent genomes and a unique biochemical reaction network. To perform their critical functions, mitochondria must maintain a distinct biochemical environment and coordinate with the cytosolic metabolic networks of the host cell. This coordination requires them to sense and control metabolites and respond to metabolic stresses. Indeed, mitochondria adopt feedback or feedforward control strategies to restrain metabolic toxicity, enable metabolic conservation, ensure stable levels of key metabolites, allow metabolic plasticity, and prevent futile cycles. A diverse panel of metabolic sensors mediates these regulatory circuits whose malfunctioning leads to inborn errors of metabolism with mild to severe clinical manifestations. In this review, we discuss the logic and molecular basis of metabolic sensing and control in mitochondria. The past research outlined recurring patterns in mitochondrial metabolic sensing and control and highlighted key knowledge gaps in this organelle that are potentially addressable with emerging technological breakthroughs.
Topics: Mitochondria; Organelles; Metabolic Networks and Pathways
PubMed: 36931256
DOI: 10.1016/j.molcel.2023.02.016 -
Physiological Reviews Jul 2024The endomembrane system consists of organellar membranes in the biosynthetic pathway [endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles] as well as... (Review)
Review
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