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1.
Unraveling the multifaceted nature of the nuclear function of mTOR.
Torres, AS, Holz, MK
Biochimica et biophysica acta. Molecular cell research. 2021;(2):118907
Abstract
Positioned at the axis between the cell and its environment, mTOR directs a wide range of cellular activity in response to nutrients, growth factors, and stress. Our understanding of the role of mTOR is evolving beyond the spatial confines of the cytosol, and its role in the nucleus becoming ever more apparent. In this review, we will address various studies that explore the role of nuclear mTOR (nmTOR) in specific cellular programs and how these pathways influence one another. To understand the emerging roles of nuclear mTOR, we discuss data and propose plausible mechanisms to offer novel ideas, hypotheses, and future research directions.
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2.
Advancing organelle genome transformation and editing for crop improvement.
Li, S, Chang, L, Zhang, J
Plant communications. 2021;(2):100141
Abstract
Plant cells contain three organelles that harbor DNA: the nucleus, plastids, and mitochondria. Plastid transformation has emerged as an attractive platform for the generation of transgenic plants, also referred to as transplastomic plants. Plastid genomes have been genetically engineered to improve crop yield, nutritional quality, and resistance to abiotic and biotic stresses, as well as for recombinant protein production. Despite many promising proof-of-concept applications, transplastomic plants have not been commercialized to date. Sequence-specific nuclease technologies are widely used to precisely modify nuclear genomes, but these tools have not been applied to edit organelle genomes because the efficient homologous recombination system in plastids facilitates plastid genome editing. Unlike plastid transformation, successful genetic transformation of higher plant mitochondrial genome transformation was tested in several research group, but not successful to date. However, stepwise progress has been made in modifying mitochondrial genes and their transcripts, thus enabling the study of their functions. Here, we provide an overview of advances in organelle transformation and genome editing for crop improvement, and we discuss the bottlenecks and future development of these technologies.
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3.
Stem cell plasticity and regenerative potential regulation through Ca2+-mediated mitochondrial nuclear crosstalk.
Paliwal, S, Fiumera, HL, Mohanty, S
Mitochondrion. 2021;:1-14
Abstract
The multi-lineage differentiation potential is one of the prominent mechanisms through which stem cells can repair damaged tissues. The regenerative potential of stem cells is the manifestation of several changes at the structural and molecular levels in stem cells that are regulated through intricate mitochondrial-nuclear interactions maintained by Ca2+ ion signaling. Despite the exhilarating evidences strengthening the versatile and indispensible role of Ca2+ in regulating mitochondrial-nuclear interactions, the extensive details of signaling mechanisms remains largely unexplored. In this review we have discussed the effect of Ca2+ ion mediated mitochondrial-nuclear interactions participating in stem plasticity and its regenerative potential.
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4.
Mitochondrial Inheritance in Phytopathogenic Fungi-Everything Is Known, or Is It?
Mendoza, H, Perlin, MH, Schirawski, J
International journal of molecular sciences. 2020;(11)
Abstract
Mitochondria are important organelles in eukaryotes that provide energy for cellular processes. Their function is highly conserved and depends on the expression of nuclear encoded genes and genes encoded in the organellar genome. Mitochondrial DNA replication is independent of the replication control of nuclear DNA and as such, mitochondria may behave as selfish elements, so they need to be controlled, maintained and reliably inherited to progeny. Phytopathogenic fungi meet with special environmental challenges within the plant host that might depend on and influence mitochondrial functions and services. We find that this topic is basically unexplored in the literature, so this review largely depends on work published in other systems. In trying to answer elemental questions on mitochondrial functioning, we aim to introduce the aspect of mitochondrial functions and services to the study of plant-microbe-interactions and stimulate phytopathologists to consider research on this important organelle in their future projects.
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5.
Mitochondrial Protein Quality Control Mechanisms.
Jadiya, P, Tomar, D
Genes. 2020;(5)
Abstract
Mitochondria serve as a hub for many cellular processes, including bioenergetics, metabolism, cellular signaling, redox balance, calcium homeostasis, and cell death. The mitochondrial proteome includes over a thousand proteins, encoded by both the mitochondrial and nuclear genomes. The majority (~99%) of proteins are nuclear encoded that are synthesized in the cytosol and subsequently imported into the mitochondria. Within the mitochondria, polypeptides fold and assemble into their native functional form. Mitochondria health and integrity depend on correct protein import, folding, and regulated turnover termed as mitochondrial protein quality control (MPQC). Failure to maintain these processes can cause mitochondrial dysfunction that leads to various pathophysiological outcomes and the commencement of diseases. Here, we summarize the current knowledge about the role of different MPQC regulatory systems such as mitochondrial chaperones, proteases, the ubiquitin-proteasome system, mitochondrial unfolded protein response, mitophagy, and mitochondria-derived vesicles in the maintenance of mitochondrial proteome and health. The proper understanding of mitochondrial protein quality control mechanisms will provide relevant insights to treat multiple human diseases.
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6.
Focusing on the nuclear and subnuclear dynamics of light and circadian signalling.
Ronald, J, Davis, SJ
Plant, cell & environment. 2019;(10):2871-2884
Abstract
Circadian clocks provide organisms the ability to synchronize their internal physiological responses with the external environment. This process, termed entrainment, occurs through the perception of internal and external stimuli. As with other organisms, in plants, the perception of light is a critical for the entrainment and sustainment of circadian rhythms. Red, blue, far-red, and UV-B light are perceived by the oscillator through the activity of photoreceptors. Four classes of photoreceptors signal to the oscillator: phytochromes, cryptochromes, UVR8, and LOV-KELCH domain proteins. In most cases, these photoreceptors localize to the nucleus in response to light and can associate to subnuclear structures to initiate downstream signalling. In this review, we will highlight the recent advances made in understanding the mechanisms facilitating the nuclear and subnuclear localization of photoreceptors and the role these subnuclear bodies have in photoreceptor signalling, including to the oscillator. We will also highlight recent progress that has been made in understanding the regulation of the nuclear and subnuclear localization of components of the plant circadian clock.
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7.
ATP, Mg2+, Nuclear Phase Separation, and Genome Accessibility.
Wright, RHG, Le Dily, F, Beato, M
Trends in biochemical sciences. 2019;(7):565-574
Abstract
Misregulation of the processes controlling eukaryotic gene expression can result in disease. Gene expression is influenced by the surrounding chromatin; hence the nuclear environment is also of vital importance. Recently, understanding of chromatin hierarchical folding has increased together with the discovery of membrane-less organelles which are distinct, dynamic liquid droplets that merge and expand within the nucleus. These 'sieve'-like regions may compartmentalize and separate functionally distinct regions of chromatin. This article aims to discuss recent studies on nuclear phase within the context of poly(ADP-ribose), ATP, and Mg2+ levels, and we propose a combinatorial complex role for these molecules in phase separation and genome regulation. We also discuss the implications of this process for gene regulation and discuss possible strategies to test this.
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8.
The Role of Cell Membrane Information Reception, Processing, and Communication in the Structure and Function of Multicellular Tissue.
Gatenby, RA
International journal of molecular sciences. 2019;(15)
Abstract
Investigations of information dynamics in eukaryotic cells focus almost exclusively on heritable information in the genome. Gene networks are modeled as "central processors" that receive, analyze, and respond to intracellular and extracellular signals with the nucleus described as a cell's control center. Here, we present a model in which cellular information is a distributed system that includes non-genomic information processing in the cell membrane that may quantitatively exceed that of the genome. Within this model, the nucleus largely acts a source of macromolecules and processes information needed to synchronize their production with temporal variations in demand. However, the nucleus cannot produce microsecond responses to acute, life-threatening perturbations and cannot spatially resolve incoming signals or direct macromolecules to the cellular regions where they are needed. In contrast, the cell membrane, as the interface with its environment, can rapidly detect, process, and respond to external threats and opportunities through the large amounts of potential information encoded within the transmembrane ion gradient. Our model proposes environmental information is detected by specialized protein gates within ion-specific transmembrane channels. When the gate receives a specific environmental signal, the ion channel opens and the received information is communicated into the cell via flow of a specific ion species (i.e., K+, Na+, Cl-, Ca2+, Mg2+) along electrochemical gradients. The fluctuation of an ion concentration within the cytoplasm adjacent to the membrane channel can elicit an immediate, local response by altering the location and function of peripheral membrane proteins. Signals that affect a larger surface area of the cell membrane and/or persist over a prolonged time period will produce similarly cytoplasmic changes on larger spatial and time scales. We propose that as the amplitude, spatial extent, and duration of changes in cytoplasmic ion concentrations increase, the information can be communicated to the nucleus and other intracellular structure through ion flows along elements of the cytoskeleton to the centrosome (via microtubules) or proteins in the nuclear membrane (via microfilaments). These dynamics add spatial and temporal context to the more well-recognized information communication from the cell membrane to the nucleus following ligand binding to membrane receptors. Here, the signal is transmitted and amplified through transduction by the canonical molecular (e.g., Mitogen Activated Protein Kinases (MAPK) pathways. Cytoplasmic diffusion allows this information to be broadly distributed to intracellular organelles but at the cost of loss of spatial and temporal information also contained in ligand binding.
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9.
Exogenous Factors May Differentially Influence the Selective Costs of mtDNA Mutations.
Aw, WC, Garvin, MR, Ballard, JWO
Advances in anatomy, embryology, and cell biology. 2019;:51-74
Abstract
In this review, we provide evidence to suggest that the cost of specific mtDNA mutations can be influenced by exogenous factors. We focus on macronutrient-mitochondrial DNA interactions as factors that may differentially influence the consequences of a change as mitochondria must be flexible in its utilization of dietary proteins, carbohydrates, and fats. To understand this fundamental dynamic, we briefly discuss the energy processing pathways in mitochondria. Next, we explore the mitochondrial functions that are initiated during energy deficiency or when cells encounter cellular stress. We consider the anterograde response (nuclear control of mitochondrial function) and the retrograde response (nuclear changes in response to mitochondrial signaling) and how this mito-nuclear crosstalk may be influenced by exogenous factors such as temperature and diet. Finally, we employ Complex I of the mitochondrial electron transport system as a case study and discuss the potential role of the dietary macronutrient ratio as a strong selective force that may shape the frequencies of mitotypes in populations and species. We conclude that this underexplored field likely has implications in the fundamental disciplines of evolutionary biology and quantitative genetics and the more biomedical fields of nutrigenomics and pharmacogenomics.
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10.
Singlet oxygen-triggered chloroplast-to-nucleus retrograde signalling pathways: An emerging perspective.
Dogra, V, Rochaix, JD, Kim, C
Plant, cell & environment. 2018;(8):1727-1738
Abstract
Singlet oxygen (1 O2 ) is a prime cause of photo-damage of the photosynthetic apparatus. The chlorophyll molecules in the photosystem II reaction center and in the light-harvesting antenna complex are major sources of 1 O2 generation. It has been thought that the generation of 1 O2 mainly takes place in the appressed regions of the thylakoid membranes, namely, the grana core, where most of the active photosystem II complexes are localized. Apart from being a toxic molecule, new evidence suggests that 1 O2 significantly contributes to chloroplast-to-nucleus retrograde signalling that primes acclimation and cell death responses. Interestingly, recent studies reveal that chloroplasts operate two distinct 1 O2 -triggered retrograde signalling pathways in which β-carotene and a nuclear-encoded chloroplast protein EXECUTER1 play essential roles as signalling mediators. The coexistence of these mediators raises several questions: their crosstalk, source(s) of 1 O2 , downstream signalling components, and the perception and reaction mechanism of these mediators towards 1 O2 . In this review, we mainly discuss the molecular genetic basis of the mode of action of these two putative 1 O2 sensors and their corresponding retrograde signalling pathways. In addition, we also propose the possible existence of an alternative source of 1 O2 , which is spatially and functionally separated from the grana core.