scholarly journals Komagataella phaffii Cue5 Piggybacks on Lipid Droplets for Its Vacuolar Degradation During Stationary Phase Lipophagy

2021 ◽  
Author(s):  
Ravinder Kumar ◽  
Ankit Shroff ◽  
Taras Y. Nazarko
Keyword(s):  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
S Phase ◽  
Ubiquitinated Protein ◽  
Selective Autophagy ◽  
Komagataella Phaffii ◽  
Ubiquitin Binding ◽  
N Starvation ◽  
Relationship Of ◽  
The Relationship

Recently, we developed Komagataella phaffii (formerly Pichia pastoris) as a model for lipophagy, the selective autophagy of lipid droplets (LDs). We found that lipophagy pathways induced by acute nitrogen (N) starvation and in stationary (S) phase have different molecular mechanisms. Moreover, both types of lipophagy are independent of Atg11, the scaffold protein that interacts with most autophagic receptors and, therefore, is essential for most types of selective autophagy in yeast. Since yeast aggrephagy, the selective autophagy of ubiquitinated protein aggregates, is also independent of Atg11 and utilizes the ubiquitin-binding receptor, Cue5, we studied the relationship of K. phaffii Cue5 with differentially induced LDs and lipophagy. While there was no relationship of Cue5 with LDs and lipophagy under N-starvation conditions, Cue5 accumulated on LDs in S-phase and degraded together with LDs via S-phase lipophagy. The accumulation of Cue5 on LDs and its degradation by S-phase lipophagy strongly depended on the ubiquitin-binding CUE domain and Prl1, the positive regulator of lipophagy 1. However, unlike Prl1, which is required for S-phase lipophagy, Cue5 was dispensable for it suggesting that Cue5 is rather a new substrate of this pathway. We propose that a similar mechanism (Prl1-dependent accumulation on LDs) might be employed by Prl1 to recruit another ubiquitin-binding protein that is essential for S-phase lipophagy.

scholarly journals Komagataella phaffii Cue5 Piggybacks on Lipid Droplets for Its Vacuolar Degradation during Stationary Phase Lipophagy

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 215
Author(s):  
Ravinder Kumar ◽  
Ankit Shroff ◽  
Taras Y. Nazarko
Keyword(s):  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
S Phase ◽  
Ubiquitinated Protein ◽  
Selective Autophagy ◽  
Komagataella Phaffii ◽  
Ubiquitin Binding ◽  
N Starvation ◽  
Relationship Of ◽  
The Relationship

Recently, we developed Komagataella phaffii (formerly Pichia pastoris) as a model for lipophagy, the selective autophagy of lipid droplets (LDs). We found that lipophagy pathways induced by acute nitrogen (N) starvation and in stationary (S) phase have different molecular mechanisms. Moreover, both types of lipophagy are independent of Atg11, the scaffold protein that interacts with most autophagic receptors and, therefore, is essential for most types of selective autophagy in yeast. Since yeast aggrephagy, the selective autophagy of ubiquitinated protein aggregates, is also independent of Atg11 and utilizes the ubiquitin-binding receptor, Cue5, we studied the relationship of K. phaffii Cue5 with differentially induced LDs and lipophagy. While there was no relationship of Cue5 with LDs and lipophagy under N-starvation conditions, Cue5 accumulated on LDs in S-phase and degraded together with LDs via S-phase lipophagy. The accumulation of Cue5 on LDs and its degradation by S-phase lipophagy strongly depended on the ubiquitin-binding CUE domain and Prl1, the positive regulator of lipophagy 1. However, unlike Prl1, which is required for S-phase lipophagy, Cue5 was dispensable for it suggesting that Cue5 is rather a new substrate of this pathway. We propose that a similar mechanism (Prl1-dependent accumulation on LDs) might be employed by Prl1 to recruit another ubiquitin-binding protein that is essential for S-phase lipophagy.

scholarly journals Nitrogen starvation and stationary phase lipophagy have distinct molecular mechanisms

2020 ◽  
Author(s):  
Ravinder Kumar ◽  
Muhammad Arifur Rahman ◽  
Taras Y. Nazarko
Keyword(s):  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Nitrogen Starvation ◽  
S Phase ◽  
Carbon Limitation ◽  
Intracellular Lipid ◽  
Selective Autophagy ◽  
The Core ◽  
Vacuole Fusion ◽  
N Starvation

AbstractIn yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g. in the stationary (S) phase). We developed the yeast, Komagataella phaffii (formerly Pichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18 and Vps15), vacuole fusion machinery (Vam7 and Ypt7) and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated the prl1 (for positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy but not N-starvation lipophagy. The prl1 defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole further supporting mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms.

scholarly journals Nitrogen Starvation and Stationary Phase Lipophagy Have Distinct Molecular Mechanisms

2020 ◽  
Vol 21 (23) ◽  
pp. 9094
Author(s):  
Ravinder Kumar ◽  
Muhammad Arifur Rahman ◽  
Taras Y. Nazarko
Keyword(s):  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Nitrogen Starvation ◽  
S Phase ◽  
Carbon Limitation ◽  
Intracellular Lipid ◽  
Selective Autophagy ◽  
The Core ◽  
Vacuole Fusion ◽  
N Starvation

In yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g., in the stationary (S) phase). We developed the yeast, Komagataella phaffii (formerly Pichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18, and Vps15), vacuole fusion machinery (Vam7 and Ypt7), and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated the prl1 (for the positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy, but not N-starvation lipophagy. The prl1 defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole, further supporting the mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Pausing controls branching between productive and non-productive pathways during initial transcription

2017 ◽  
Author(s):  
David Dulin ◽  
David L. V. Bauer ◽  
Anssi M. Malinen ◽  
Jacob J. W. Bakermans ◽  
Martin Kaller ◽  
...  
Keyword(s):  
Single Molecule ◽  
Transcription Initiation ◽  
Rna Synthesis ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Single Molecule Fret ◽  
Bacterial Rna ◽  
Tightly Coupled ◽  
Relationship Of ◽  
The Relationship

AbstractTranscription in bacteria is controlled by multiple molecular mechanisms that precisely regulate gene expression. Recently, initial RNA synthesis by the bacterial RNA polymerase (RNAP) has been shown to be interrupted by pauses; however, the pausing determinants and the relationship of pausing with productive and abortive RNA synthesis remain poorly understood. Here, we employed single-molecule FRET and biochemical analysis to disentangle the pausing-related pathways of bacterial initial transcription. We present further evidence that region σ3.2 constitutes a barrier after the initial transcribing complex synthesizes a 6-nt RNA (ITC6), halting transcription. We also show that the paused ITC6 state acts as a checkpoint that directs RNAP, in an NTP-dependent manner, to one of three competing pathways: productive transcription, abortive RNA release, or a new unscrunching/scrunching pathway that blocks transcription initiation. Our results show that abortive RNA release and DNA unscrunching are not as tightly coupled as previously thought.

A study of leaf-senescence genes in rice based on a combination of genomics, proteomics and bioinformatics

2020 ◽  
Author(s):  
Erhui Xiong ◽  
Zhiyong Li ◽  
Chen Zhang ◽  
Jing Zhang ◽  
Ye Liu ◽  
...  
Keyword(s):  
Leaf Senescence ◽  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Chlorophyll Synthesis ◽  
Research Progress ◽  
Rice Leaf ◽  
Acid Pathway ◽  
Relationship Of ◽  
The Relationship ◽  
Synthesis And Degradation

Abstract Leaf senescence is a highly complex, genetically regulated and well-ordered process with multiple layers and pathways. Delaying leaf senescence would help increase grain yields in rice. Over the past 15 years, more than 100 rice leaf-senescence genes have been cloned, greatly improving the understanding of leaf senescence in rice. Systematically elucidating the molecular mechanisms underlying leaf senescence will provide breeders with new tools/options for improving many important agronomic traits. In this study, we summarized recent reports on 125 rice leaf-senescence genes, providing an overview of the research progress in this field by analyzing the subcellular localizations, molecular functions and the relationship of them. These data showed that chlorophyll synthesis and degradation, chloroplast development, abscisic acid pathway, jasmonic acid pathway, nitrogen assimilation and ROS play an important role in regulating the leaf senescence in rice. Furthermore, we predicted and analyzed the proteins that interact with leaf-senescence proteins and achieved a more profound understanding of the molecular principles underlying the regulatory mechanisms by which leaf senescence occurs, thus providing new insights for future investigations of leaf senescence in rice.

dna flow cytometry of canine mammary tumours: the relationship of dna ploidy and S-phase fraction to clinical and histological features

1995 ◽  
Vol 58 (3) ◽  
pp. 238-243 ◽  
Author(s):  
M.D Péreze Alenza ◽  
G.R Rutteman ◽  
N.J Kuipers-Dijkshoorn ◽  
L Peña ◽  
A Montoya ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Dna Ploidy ◽  
S Phase ◽  
Phase Fraction ◽  
Dna Flow Cytometry ◽  
Histological Features ◽  
Mammary Tumours ◽  
Relationship Of ◽  
The Relationship

scholarly journals Unraveling the Relationship of Asthma and COVID-19

2021 ◽  
Vol 11 (12) ◽  
pp. 1374
Author(s):  
Agamemnon Bakakos ◽  
Petros Bakakos ◽  
Nikoletta Rovina
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Asthma Severity ◽  
Current Evidence ◽  
Asthma Exacerbations ◽  
Inflammatory Phenotypes ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities have assessed whether asthma represents a risk factor for SARS-CoV2 infection and/or more severe course of the disease. This review covers the current evidence on the prevalence of asthma in COVID-19 and its association with susceptibility to and severity of SARS-CoV2 infection. It will examine the possible role of underlying asthma severity in COVID-19 related outcomes as well as the molecular mechanisms involved in the co-existence of these entities. The possible role of asthma inflammatory phenotypes will also be evaluated. Finally, the impact of asthma comorbidities and the implications of asthma medication on COVID-19 will be addressed.

scholarly journals Fine-tuning of SUMOylation modulates drought tolerance

2021 ◽  
Author(s):  
Qingmei Guan ◽  
Xuewei Li ◽  
Shuang-Xi Zhou ◽  
Liyuan Lu ◽  
Huan Dang ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Molecular Mechanisms ◽  
Plant Biology ◽  
Fine Tuning ◽  
Wild Type ◽  
Tight Control ◽  
Drought Tolerant ◽  
Relationship Of ◽  
The Relationship

SUMOylation is involved in various aspects of plant biology, including drought stress. However, the relationship between SUMOylation and drought stress tolerance is complex; whether SUMOylation has a crosstalk with ubiquitination in response to drought stress remains largely unclear. In this study, we found that both increased and decreased SUMOylation led to increased survival of apple (Malus × domestica) under drought stress: both transgenic MdSUMO2A overexpressing (OE) plants and MdSUMO2 RNAi plants exhibited enhanced drought tolerance. We further confirmed that MdDREB2A is one of the MdSUMO2 targets. Both transgenic MdDREB2A OE and MdDREB2AK192R OE plants (which lacked the key site of SUMOylation by MdSUMO2A) were more drought tolerant than wild-type plants. However, MdDREB2AK192R OE plants had a much higher survival rate than MdDREB2A OE plants. We further showed SUMOylated MdDREB2A was conjugated with ubiquitin by MdRNF4 under drought stress, thereby triggering its protein degradation. In addition, MdRNF4 RNAi plants were more tolerant to drought stress. These results revealed the molecular mechanisms that underlie the relationship of SUMOylation with drought tolerance and provided evidence for the tight control of MdDREB2A accumulation under drought stress mediated by SUMOylation and ubiquitination.

MRI Assessment of Peritumoral Brain Edema in Human Astrocytomas: Correlation with Angiogenesis Biomarkers

2005 ◽  
Vol 18 (1) ◽  
pp. 37-41
Author(s):  
G.Q. Wei ◽  
H.D. He ◽  
W.P. Liu ◽  
H.N. Zhen ◽  
J. Zhao ◽  
...  
Keyword(s):  
Brain Edema ◽  
Molecular Mechanisms ◽  
Mass Effect ◽  
Vascular Endothelial ◽  
Imaging Characteristics ◽  
Peritumoral Brain Edema ◽  
Relationship Of ◽  
Endothelial Growth Factor ◽  
The Relationship ◽  
Human Astrocytomas

Mass effect due to peritumoral brain edema (PTBE) is one of the most common imaging characteristics encountered in glial tumors. The severity and variety of the PTBE may increase the difficulties of cancer treatment. However, its pathogenesis is not well documented. Recently, more attention has been paid to vascular endothelial growth factor (VEGF), the polypeptides mediating tumor angiogenesis and microvascular permeability. The purpose of this study was to investigate PTBE index in astrocytomas obtained from MRI and its correlation with angiogenesis biomarkers, VEGF and microvessel density. Our results demonstrated that PTBE in human astrocytomas correlated with both VEGF expression and vessel density. The relationship of PTBE with angiogenesis biomarkers allows a better understanding its molecular mechanisms, and may have implications for clinical management of brain edema associated with human astrocytomas.

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