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Article ; Online: ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division.

Boutry, Maxime / Kim, Peter K

2021 Volume 12, Issue 1, Page(s) 5354

Abstract: Mitochondrial division is not an autonomous event but involves multiple organelles, including the endoplasmic reticulum (ER) and lysosomes. Whereas the ER drives the constriction of mitochondrial membranes, the role of lysosomes in mitochondrial division ...

Abstract	Mitochondrial division is not an autonomous event but involves multiple organelles, including the endoplasmic reticulum (ER) and lysosomes. Whereas the ER drives the constriction of mitochondrial membranes, the role of lysosomes in mitochondrial division is not known. Here, using super-resolution live-cell imaging, we investigate the recruitment of lysosomes to the site of mitochondrial division. We find that the ER recruits lysosomes to the site of division through the interaction of VAMP-associated proteins (VAPs) with the lysosomal lipid transfer protein ORP1L to induce a three-way contact between the ER, lysosome, and the mitochondrion. We also show that ORP1L might transport phosphatidylinositol-4-phosphate (PI(4)P) from lysosomes to mitochondria, as inhibiting its transfer or depleting PI(4)P at the mitochondrial division site impairs fission, demonstrating a direct role for PI(4)P in the division process. Our findings support a model where the ER recruits lysosomes to act in concert at the fission site for the efficient division of mitochondria.
MeSH term(s)	Animals ; COS Cells ; Cell Line, Tumor ; Chlorocebus aethiops ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Humans ; Lysosomes/metabolism ; Microscopy, Confocal/methods ; Mitochondria/metabolism ; Mitochondrial Dynamics ; Phosphatidylinositol Phosphates/metabolism ; RNA Interference ; Receptors, Steroid/genetics ; Receptors, Steroid/metabolism ; Signal Transduction ; rab GTP-Binding Proteins/genetics ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Phosphatidylinositol Phosphates ; Receptors, Steroid ; oxysterol binding protein ; phosphatidylinositol 4-phosphate ; rab7 protein (152989-05-4) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2021-09-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-25621-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bilateral Nonarteritic Anterior Ischemic Optic Neuropathy Associated With Bleeding Diathesis and COVID-Associated Coagulopathy.

Sriram, Aishwarya / Kim, Peter K / Palaiodimos, Leonidas / Parnes, Gregory J / Mbekeani, Joyce N

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

2024

Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1189901-3
ISSN	1536-5166 ; 1070-8022
ISSN (online)	1536-5166
ISSN	1070-8022
DOI	10.1097/WNO.0000000000002173
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Article ; Online: Pexophagy: A Model for Selective Autophagy.

Germain, Kyla / Kim, Peter K

International journal of molecular sciences

2020 Volume 21, Issue 2

Abstract: The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual ... ...

Abstract	The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual substrates are degraded during selective autophagy in response to both extracellular and intracellular cues is not well understood. The aim of this review is to highlight pexophagy, the autophagic degradation of peroxisomes, as a model for selective autophagy. Peroxisomes are dynamic organelles whose abundance is rapidly modulated in response to metabolic demands. Peroxisomes are routinely turned over by pexophagy for organelle quality control yet can also be degraded by pexophagy in response to external stimuli such as amino acid starvation or hypoxia. This review discusses the molecular machinery and regulatory mechanisms governing substrate selectivity during both quality-control pexophagy and pexophagy in response to external stimuli, in yeast and mammalian systems. We draw lessons from pexophagy to infer how the cell may coordinate the degradation of individual substrates by selective autophagy across different cellular cues.
MeSH term(s)	Animals ; Autophagy/physiology ; Macroautophagy/physiology ; Models, Theoretical ; Peroxisomes/metabolism
Language	English
Publishing date	2020-01-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21020578
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Article ; Online: Upregulated pexophagy limits the capacity of selective autophagy.

Germain, Kyla / So, Raphaella W L / DiGiovanni, Laura F / Watts, Joel C / Bandsma, Robert H J / Kim, Peter K

Nature communications

2024 Volume 15, Issue 1, Page(s) 375

Abstract: Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but ... ...

Abstract	Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but whether these pathways can influence one another remains unknown. We address this question using pexophagy, the autophagic degradation of peroxisomes, as a model. We show in cells that upregulated pexophagy impairs the selective autophagy of both mitochondria and protein aggregates by exhausting the autophagy initiation factor, ULK1. We confirm this finding in cell models of the pexophagy-mediated form of Zellweger Spectrum Disorder, a disease characterized by peroxisome dysfunction. Further, we extend the generalizability of limited selective autophagy by determining that increased protein aggregate degradation reciprocally reduces pexophagy using cell models of Parkinson's Disease and Huntington's Disease. Our findings suggest that the degradative capacity of selective autophagy can become limited by an increase in one substrate.
MeSH term(s)	Humans ; Macroautophagy/genetics ; Autophagy/genetics ; Huntington Disease/genetics ; Mitochondria/genetics ; Parkinson Disease/genetics
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44005-4
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Article ; Online: Association of thoracic cage fractures and pericardial effusion in blunt trauma.

Offenbacher, Joseph / Kim, Peter K / Nguyen, Vincent / Meltzer, James A

The American journal of emergency medicine

2021 Volume 50, Page(s) 729–732

Abstract: Background: Several case reports suggest that penetrating thoracic cage fractures are an important cause for hemopericardium and cardiac tamponade following blunt trauma. However, the prevalence of this mechanism of injury is not fully known, and ... ...

Abstract	Background: Several case reports suggest that penetrating thoracic cage fractures are an important cause for hemopericardium and cardiac tamponade following blunt trauma. However, the prevalence of this mechanism of injury is not fully known, and considering this association may provide a better understanding of the utility of cardiac component of the FAST (Focused Assessment with Sonography for Trauma). Objective: To determine the association of thoracic cage fractures and pericardial effusion in patients with blunt trauma. Methods: We performed a retrospective, multicenter cohort study using the Trauma Quality Improvement Program (TQIP) database (2015-2017) of adults ≥18 years of age whose mechanism of injury was either a fall or motor vehicle accident. Thoracic cage fractures were defined as any rib or sternum fracture. The primary outcome was the presence of pericardial effusion. Confounding variables were accounted for using multivariable logistic regression. Results: We included 1,673,704 patients in the study; 226,896 (14%) patients had at least one thoracic cage fracture. A pericardial effusion was present in 4923 (0.3%) patients. When a thoracic cage fracture was present, the odds of having a pericardial effusion was significantly higher (adjusted Odds Ratio [aOR] 6.5 [95% CI: 6.1-7.0]). Patients with left and right-sided rib fractures had similar odds of a pericardial effusion (aOR 1.2 [95% CI 1.04-1.4]). Sternal fractures carried the highest odds of having a pericardial effusion (aOR 11.1 [9.9-12.3]). Conclusion: Thoracic cage fractures secondary to blunt trauma represent a significant independent risk factor for the development of a pericardial effusion. Our findings lend support for the mechanism of bony injuries causing penetrating cardiac trauma. Given these findings, and the fact that many thoracic cage fractures are detected after the initial evaluation, we support maintaining the cardiac view in the FAST examination for all blunt trauma patients.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Focused Assessment with Sonography for Trauma ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pericardial Effusion/diagnosis ; Pericardial Effusion/epidemiology ; Pericardial Effusion/etiology ; Prevalence ; Retrospective Studies ; Rib Fractures/complications ; Rib Fractures/diagnostic imaging ; Risk Factors ; Sternum/injuries ; Wounds, Nonpenetrating/complications ; Wounds, Nonpenetrating/diagnostic imaging ; Young Adult
Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2021.08.052
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Zs.A 2005: Show issues

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Article ; Online: Arf1-PI4KIIIβ positive vesicles regulate PI(3)P signaling to facilitate lysosomal tubule fission.

Boutry, Maxime / DiGiovanni, Laura F / Demers, Nicholas / Fountain, Aaron / Mamand, Sami / Botelho, Roberto J / Kim, Peter K

The Journal of cell biology

2023 Volume 222, Issue 9

Abstract: Formation and fission of tubules from autolysosomes, endolysosomes, or phagolysosomes are required for lysosome reformation. However, the mechanisms governing these processes in these different lysosomal organelles are poorly understood. Thus, the role ... ...

Abstract	Formation and fission of tubules from autolysosomes, endolysosomes, or phagolysosomes are required for lysosome reformation. However, the mechanisms governing these processes in these different lysosomal organelles are poorly understood. Thus, the role of phosphatidylinositol-4-phosphate (PI(4)P) is unclear as it was shown to promote the formation of tubules from phagolysosomes but was proposed to inhibit tubule formation on autolysosomes because the loss of PI4KIIIβ causes extensive lysosomal tubulation. Using super-resolution live-cell imaging, we show that Arf1-PI4KIIIβ positive vesicles are recruited to tubule fission sites from autolysosomes, endolysosomes, and phagolysosomes. Moreover, we show that PI(4)P is required to form autolysosomal tubules and that increased lysosomal tubulation caused by loss of PI4KIIIβ represents impaired tubule fission. At the site of fission, we propose that Arf1-PI4KIIIβ positive vesicles mediate a PI(3)P signal on lysosomes in a process requiring the lipid transfer protein SEC14L2. Our findings indicate that Arf1-PI4KIIIβ positive vesicles and their regulation of PI(3)P are critical components of the lysosomal tubule fission machinery.
MeSH term(s)	Lysosomes/metabolism ; Signal Transduction ; ADP-Ribosylation Factor 1/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/metabolism
Chemical Substances	phosphatidylinositol 3-phosphate ; ADP-Ribosylation Factor 1 (EC 3.6.5.2) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-)
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202205128
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Article ; Online: Hyperspectral super-resolution imaging with far-red emitting fluorophores using a thin-film tunable filter.

Vissa, Adriano / Giuliani, Maximiliano / Kim, Peter K / Yip, Christopher M

The Review of scientific instruments

2020 Volume 91, Issue 12, Page(s) 123703

Abstract: New innovations in single-molecule localization microscopy (SMLM) have revolutionized optical imaging, enabling the characterization of biological structures and interactions with unprecedented detail and resolution. However, multi-color or hyperspectral ...

Abstract	New innovations in single-molecule localization microscopy (SMLM) have revolutionized optical imaging, enabling the characterization of biological structures and interactions with unprecedented detail and resolution. However, multi-color or hyperspectral SMLM can pose particular challenges which affect image quality and data interpretation, such as unequal photophysical performance of fluorophores and non-linear image registration issues, which arise as two emission channels travel along different optical paths to reach the detector. In addition, using evanescent-wave based approaches (Total Internal Reflection Fluorescence: TIRF) where beam shape, decay depth, and power density are important, different illumination wavelengths can lead to unequal imaging depth across multiple channels on the same sample. A potential useful approach would be to use a single excitation wavelength to perform hyperspectral localization imaging. We report herein on the use of a variable angle tunable thin-film filter to spectrally isolate far-red emitting fluorophores. This solution was integrated into a commercial microscope platform using an open-source hardware design, enabling the rapid acquisition of SMLM images arising from fluorescence emission captured within ∼15 nm to 20 nm spectral windows (or detection bands). By characterizing intensity distributions, average intensities, and localization frequency through a range of spectral windows, we investigated several far-red emitting fluorophores and identified an optimal fluorophore pair for two-color SMLM using this method. Fluorophore crosstalk between the different spectral windows was assessed by examining the effect of varying the photon output thresholds on the localization frequency and fraction of data recovered. The utility of this approach was demonstrated by hyper-spectral super-resolution imaging of the interaction between the mitochondrial protein, TOM20, and the peroxisomal protein, PMP70.
Language	English
Publishing date	2020-11-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	209865-9
ISSN	1089-7623 ; 0034-6748
ISSN (online)	1089-7623
ISSN	0034-6748
DOI	10.1063/1.5143319
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Article ; Online: Gemella morbillorum

Romero-Velez, Gustavo / Pereira, Xavier / Narula, Anil / Kim, Peter K

BMJ case reports

2020 Volume 13, Issue 1

Abstract: A 66-year-old man presented with upper back cellulitis and imaging findings consistent with a necrotising soft tissue infection. He was started on broad-spectrum intravenous antibiotics and was taken to the operating room for immediate surgical ... ...

Abstract	A 66-year-old man presented with upper back cellulitis and imaging findings consistent with a necrotising soft tissue infection. He was started on broad-spectrum intravenous antibiotics and was taken to the operating room for immediate surgical debridement. On postoperative day 5, the culture was noted to be growing
MeSH term(s)	Administration, Intravenous ; Aged ; Anti-Bacterial Agents/therapeutic use ; Debridement ; Diagnosis, Differential ; Fasciitis, Necrotizing/drug therapy ; Fasciitis, Necrotizing/microbiology ; Gemella/isolation & purification ; Gram-Positive Bacterial Infections/drug therapy ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Male ; Torso/microbiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-01-06
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2019-231727
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Article: The future of general surgery.

Kim, Peter K

Bulletin of the American College of Surgeons

2011 Volume 96, Issue 2, Page(s) 60–61

MeSH term(s)	Forecasting ; General Surgery/trends ; United States
Language	English
Publishing date	2011-02
Publishing country	United States
Document type	Letter
ZDB-ID	390409-x
ISSN	0002-8045
ISSN	0002-8045
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Zs.B 513: Show issues

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Article: Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals.

Hua, Rong / Kim, Peter K

Biochimica et biophysica acta

2016 Volume 1863, Issue 5, Page(s) 881–891

Abstract: Peroxisomes are dynamic organelles that can adjust their size and number in response to cellular demand and environmental stimuli. They can propagate from pre-existing peroxisomes through growth and division, as well as de novo from the endoplasmic ... ...

Abstract	Peroxisomes are dynamic organelles that can adjust their size and number in response to cellular demand and environmental stimuli. They can propagate from pre-existing peroxisomes through growth and division, as well as de novo from the endoplasmic reticulum (ER). However, to what extend that these two distinct peroxisome biogenesis pathways are involved in maintaining peroxisome numbers in cycling cells is unclear. Recent studies in yeast suggest that the ER plays a direct role in the maintenance of peroxisomes. However, the role of the ER in mammalian system is under debate. In this review, we outline the recent progress in understanding the biogenesis of mammalian peroxisomes. We herein discuss some of the discrepancies in the literature and the outstanding questions in the field.
MeSH term(s)	Animals ; Endoplasmic Reticulum/chemistry ; Endoplasmic Reticulum/metabolism ; Gene Expression Regulation ; Humans ; Lipoproteins/chemistry ; Lipoproteins/genetics ; Lipoproteins/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mitochondria/chemistry ; Mitochondria/metabolism ; Organelle Biogenesis ; Peroxins ; Peroxisomes/chemistry ; Peroxisomes/metabolism ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Transport ; Signal Transduction
Chemical Substances	Lipoproteins ; Membrane Proteins ; PEX16 protein, human ; Peroxins ; Pex3 protein, human ; Protein Isoforms ; PEX19 protein, human (157153-79-2)
Language	English
Publishing date	2016-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2015.09.026
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