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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 -
Kidney International Jun 2019Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered... (Review)
Review
Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. The UPR pathway in the ER also regulates mitochondrial metabolic status, indicating the pathophysiological significance of organelle crosstalk between the ER and mitochondria via the UPR pathway. In recent years, it has become obvious that communication among organelles also is conducted through direct interactions at membrane contact sites (MCSs). Organelles exchange materials including lipids, ions, and proteins at the MCS. Accordingly, alterations to these networks, such as impaired ER-mitochondria MCSs, have been linked to several diseases such as neurodegeneration and diabetes. In this review, we describe the roles of organelles in kidney diseases and the mechanisms underlying organelle communication at the MCS, and especially at the mitochondria-associated ER membrane. Potential treatment options that are focused on organelle crosstalk are discussed, in addition to the relationship between this phenomenon and various diseases, especially kidney diseases.
Topics: Animals; Disease Progression; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Intracellular Membranes; Kidney; Kidney Diseases; Lysosomes; Mitochondria; Peroxisomes; Unfolded Protein Response
PubMed: 30878214
DOI: 10.1016/j.kint.2018.11.035 -
ACS Applied Materials & Interfaces May 2021Subcellular organelles are the cornerstones of cells, and destroying them will cause cell dysfunction and even death. Therefore, realizing precise organelle targeting of... (Review)
Review
Subcellular organelles are the cornerstones of cells, and destroying them will cause cell dysfunction and even death. Therefore, realizing precise organelle targeting of photosensitizers (PSs) can help reduce PS dosage, minimize side effects, avoid drug resistance, and enhance therapeutic efficacy in photodynamic therapy (PDT). Organelle-targeted PSs provide a new paradigm for the construction of the next generation of PSs and may provide implementable strategies for future precision medicine. In this Review, the recent targeting strategies of different organelles and the corresponding design principles of molecular and nanostructured PSs are summarized and discussed. The current challenges and opportunities in organelle-targeted PDT are also presented.
Topics: Drug Delivery Systems; Humans; Organelles; Photochemotherapy; Photosensitizing Agents
PubMed: 33900741
DOI: 10.1021/acsami.1c02019 -
Chemical Communications (Cambridge,... Aug 2021Over the past ten years, advances in the field of organelle-targeted photothermal therapy (PTT) have stimulated the rapid development of organelle-targeted PTT agents as... (Review)
Review
Over the past ten years, advances in the field of organelle-targeted photothermal therapy (PTT) have stimulated the rapid development of organelle-targeted PTT agents as anticancer therapeutic agents. However, to the best of our knowledge, no comprehensive review of organelle-targeted PTT agents has been reported thus far. In this article, we have provided a structured approach for describing the different types and properties of each organelle-targeted PTT agent as well as the potential future therapeutic applications that were classified by their target organelles. Representative agents that have been used in the field of PTT since 2010 have been summarized and the most recent advances in improving the therapeutic efficacy across various types of cancers have also been highlighted.
Topics: Antineoplastic Agents; Humans; Neoplasms; Organelles; Photothermal Therapy
PubMed: 34286722
DOI: 10.1039/d1cc02168k -
Journal of Genetics and Genomics = Yi... Apr 2019Most cellular processes descend into failure during aging. While a large collection of longevity pathways has been identified in the past decades, the mechanism for... (Review)
Review
Most cellular processes descend into failure during aging. While a large collection of longevity pathways has been identified in the past decades, the mechanism for age-related decline of cellular homeostasis and organelle function remains largely unsolved. It is known that many organelles undergo structural and functional changes during normal aging, which significantly contributes to the decline of tissue function at old ages. Since recent studies have revealed an emerging role of organelles as regulatory hubs in maintaining cellular homeostasis, understanding of organelle aging will provide important insights into the cellular basis of organismal aging. Here we review current progress on the characterization of age-dependent structural and functional alterations in the more well-studied organelles, as well as the known mechanisms governing organelle aging in model organisms, with a special focus on the fruit fly Drosophila melanogaster.
Topics: Aging; Animals; Drosophila melanogaster; Humans; Organelles
PubMed: 31080045
DOI: 10.1016/j.jgg.2019.03.011 -
Annual Review of Analytical Chemistry... Jun 2022Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same... (Review)
Review
Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same organelles may have different functions or properties not only within different cell populations of a tissue but also within the same cell. Dysfunction or altered function affects the organelle itself and may also lead to malignancies or undesirable cell death. To understand cellular function or dysfunction, it is therefore necessary to analyze cellular components at the single-organelle level. Here, we review the recent advances in analyzing cellular function at single-organelle resolution using high-parameter flow cytometry or multicolor confocal microscopy. We focus on the analysis of mitochondria, as they are organelles at the crossroads of various cellular signaling pathways and functions. However, most of the applied methods/technologies are transferable to any other organelle, such as the endoplasmic reticulum, lysosomes, or peroxisomes.
Topics: Endoplasmic Reticulum; Lysosomes; Microscopy, Confocal; Mitochondria; Peroxisomes
PubMed: 35303775
DOI: 10.1146/annurev-anchem-061020-111722 -
Journal of Inherited Metabolic Disease Jan 2020Peroxisomes are multifunctional, dynamic, membrane-bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and... (Review)
Review
Peroxisomes are multifunctional, dynamic, membrane-bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and development. Important roles for peroxisomes in signaling and the fine-tuning of cellular processes are emerging, which integrate them in a complex network of interacting cellular compartments. Like many other organelles, peroxisomes communicate through membrane contact sites. For example, peroxisomal growth, positioning, and lipid metabolism involves contacts with the endoplasmic reticulum (ER). Here, we discuss the most recent findings on peroxisome-organelle interactions including peroxisome-ER interplay at membrane contacts sites, and functional interplay with mitochondria, lysosomes, and lipid droplets in mammalian cells. We address tether proteins, metabolic cooperation, and the impact of peroxisome interactions on human health and disease.
Topics: Animals; Disease; Endoplasmic Reticulum; Health; Humans; Lipid Droplets; Lipid Metabolism; Lysosomes; Membrane Proteins; Mitochondria; Mitochondrial Membranes; Organelles; Peroxisomes; Signal Transduction
PubMed: 30864148
DOI: 10.1002/jimd.12083 -
Neuron Aug 2022The defining evolutionary feature of eukaryotic cells is the emergence of membrane-bound organelles. Compartmentalization allows each organelle to maintain a spatially,... (Review)
Review
The defining evolutionary feature of eukaryotic cells is the emergence of membrane-bound organelles. Compartmentalization allows each organelle to maintain a spatially, physically, and chemically distinct environment, which greatly bolsters individual organelle function. However, the activities of each organelle must be balanced and are interdependent for cellular homeostasis. Therefore, properly regulated interactions between organelles, either physically or functionally, remain critical for overall cellular health and behavior. In particular, neuronal homeostasis depends heavily on the proper regulation of organelle function and cross talk, and deficits in these functions are frequently associated with diseases. In this review, we examine the emerging role of organelle contacts in neurological diseases and discuss how the disruption of contacts contributes to disease pathogenesis. Understanding the molecular mechanisms underlying the formation and regulation of organelle contacts will broaden our knowledge of their role in health and disease, laying the groundwork for the development of new therapies targeting interorganelle cross talk and function.
Topics: Endoplasmic Reticulum; Homeostasis; Organelles
PubMed: 35561676
DOI: 10.1016/j.neuron.2022.04.020 -
Physiology (Bethesda, Md.) May 2023Organelles are membrane-lined structures that compartmentalize subcellular biochemical functions. Therefore, interorganelle communication is crucial for cellular... (Review)
Review
Organelles are membrane-lined structures that compartmentalize subcellular biochemical functions. Therefore, interorganelle communication is crucial for cellular responses that require the coordination of such functions. Multiple principles govern interorganelle interactions, which arise from the complex nature of organelles: position, multilingualism, continuity, heterogeneity, proximity, and bidirectionality, among others. Given their importance, alterations in organelle communication have been linked to many diseases. Among the different types of contacts, endoplasmic reticulum mitochondria interactions are the best known; however, mounting evidence indicates that other organelles also have something to say in the pathophysiological conversation.
Topics: Humans; Mitochondria; Endoplasmic Reticulum; Organelles
PubMed: 36856309
DOI: 10.1152/physiol.00024.2022 -
Theranostics 2022Organelles are tiny structures with specific functions in eukaryotic cells. Since they are covered with membranes, different organelles can perform biological processes... (Review)
Review
Organelles are tiny structures with specific functions in eukaryotic cells. Since they are covered with membranes, different organelles can perform biological processes that are incompatible. Organelles can also actively communicate with each other to maintain cellular homeostasis the vesicular trafficking pathways and membrane contact sites (MCSs), which allow the exchange of metabolites and other information required for normal cellular physiology. An imbalance in organelle interactions may result in multiple pathological processes. Growing evidence shows that abnormal organelle communication contributes to cellular senescence and is associated with organ aging. However, the key role of organelle interactions in aging has not yet been broadly reviewed and fully investigated. In this review, we summarize the role of organelle interactions in cellular senescence, and highlight their relevance for cellular calcium homeostasis, protein and lipid homeostasis, and mitochondrial quality control. Our review reveals important mechanisms of organelle interactions in cellular senescence and provides important clues for intervention strategies from a new perspective.
Topics: Cellular Senescence; Homeostasis; Mitochondria; Mitochondrial Membranes; Organelles
PubMed: 35265219
DOI: 10.7150/thno.70588