scholarly journals Sestrin2 Phosphorylation by ULK1 Induces Autophagic Degradation of Mitochondria Damaged by Copper-Induced Oxidative Stress

2020 ◽  
Vol 21 (17) ◽  
pp. 6130 ◽  
Author(s):  
Heejeong Kim ◽  
Byeong Tak Jeon ◽  
Isaac M. Kim ◽  
Sydney J. Bennett ◽  
Carolyn M. Lorch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heavy Metal Stress ◽  
Adaptor Proteins ◽  
Metal Stress ◽  
Hek293 Cells ◽  
Phosphorylation Sites ◽  
Autophagic Degradation ◽  
Inducible Protein ◽  
Stress Sensing

Selective autolysosomal degradation of damaged mitochondria, also called mitophagy, is an indispensable process for maintaining integrity and homeostasis of mitochondria. One well-established mechanism mediating selective removal of mitochondria under relatively mild mitochondria-depolarizing stress is PINK1-Parkin-mediated or ubiquitin-dependent mitophagy. However, additional mechanisms such as LC3-mediated or ubiquitin-independent mitophagy induction by heavy environmental stress exist and remain poorly understood. The present study unravels a novel role of stress-inducible protein Sestrin2 in degradation of mitochondria damaged by transition metal stress. By utilizing proteomic methods and studies in cell culture and rodent models, we identify autophagy kinase ULK1-mediated phosphorylation sites of Sestrin2 and demonstrate Sestrin2 association with mitochondria adaptor proteins in HEK293 cells. We show that Ser-73 and Ser-254 residues of Sestrin2 are phosphorylated by ULK1, and a pool of Sestrin2 is strongly associated with mitochondrial ATP5A in response to Cu-induced oxidative stress. Subsequently, this interaction promotes association with LC3-coated autolysosomes to induce degradation of mitochondria damaged by Cu-induced ROS. Treatment of cells with antioxidants or a Cu chelator significantly reduces Sestrin2 association with mitochondria. These results highlight the ULK1-Sestrin2 pathway as a novel stress-sensing mechanism that can rapidly induce autophagic degradation of mitochondria under severe heavy metal stress.

scholarly journals Heme oxygenase-2 (HO-2) binds and buffers labile heme, which is largely oxidized, in human embryonic kidney cells

2021 ◽  
Author(s):  
David A Hanna ◽  
Courtney M Moore ◽  
Liu Liu ◽  
Xiaojing Yuan ◽  
Angela S Fleischhacker ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Physiological Function ◽  
Hek293 Cells ◽  
Kidney Cells ◽  
Human Embryonic Kidney ◽  
Human Embryonic Kidney Cells ◽  
Heme Oxygenases ◽  
Heme Trafficking ◽  
Ferrous Heme

Heme oxygenases (HO) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin and excreted. Humans express two isoforms: inducible HO-1, which is up-regulated in response to various stressors, including excess heme, and constitutive HO-2. While much is known about the regulation and physiological function of HO-1, comparatively little is known about the role of HO-2 in regulating heme homeostasis. The biochemical necessity for expressing constitutive HO-2 is largely dependent on whether heme is sufficiently abundant and accessible as a substrate under conditions in which HO-1 is not induced. By measuring labile heme, total heme, and bilirubin in human embryonic kidney HEK293 cells with silenced or over-expressed HO-2, and various HO-2 mutant alleles, we found that endogenous heme is too limiting to support HO-2 catalyzed heme degradation. Rather, we discovered that a novel role for HO-2 is to bind and buffer labile heme. Taken together, in the absence of excess heme, we propose that HO-2 regulates heme homeostasis by acting as a heme buffering factor in control of heme bioavailability. When heme is in excess, HO-1 is induced and both HO-2 and HO-1 can provide protection from heme toxicity by enzymatically degrading it. Our results explain why catalytically inactive mutants of HO-2 are cytoprotective against oxidative stress. Moreover, the change in bioavailable heme due to HO-2 overexpression, which selectively binds ferric over ferrous heme, is consistent with the labile heme pool being oxidized, thereby providing new insights into heme trafficking and signaling.

scholarly journals Role of nitric oxide in plant responses to heavy metal stress: exogenous application versus endogenous production

2019 ◽  
Vol 70 (17) ◽  
pp. 4477-4488 ◽  
Author(s):  
Laura C Terrón-Camero ◽  
M Ángeles Peláez-Vico ◽  
Coral Del-Val ◽  
Luisa M Sandalio ◽  
María C Romero-Puertas
Keyword(s):  
Nitric Oxide ◽  
Heavy Metals ◽  
Heavy Metal ◽  
Human Health Risk ◽  
Heavy Metal Stress ◽  
Metal Stress ◽  
Future Research ◽  
Plant Responses ◽  
Research Perspectives

Abstract Anthropogenic activities, such as industrial processes, mining, and agriculture, lead to an increase in heavy metal concentrations in soil, water, and air. Given their stability in the environment, heavy metals are difficult to eliminate and can constitute a human health risk by entering the food chain through uptake by crop plants. An excess of heavy metals is toxic for plants, which have various mechanisms to prevent their accumulation. However, once metals enter the plant, oxidative damage sometimes occurs, which can lead to plant death. Initial production of nitric oxide (NO), which may play a role in plant perception, signalling, and stress acclimation, has been shown to protect against heavy metals. Very little is known about NO-dependent mechanisms downstream from signalling pathways in plant responses to heavy metal stress. In this review, using bioinformatic techniques, we analyse studies of the involvement of NO in plant responses to heavy metal stress, its possible role as a cytoprotective molecule, and its relationship with reactive oxygen species. Some conclusions are drawn and future research perspectives are outlined to further elucidate the signalling mechanisms underlying the role of NO in plant responses to heavy metal stress.

Role of Nitric Oxide in Overcoming Heavy Metal Stress

2020 ◽  
pp. 214-237
Author(s):  
Pradyumna Kumar Singh ◽  
Madhu Tiwari ◽  
Maria Kidwai ◽  
Dipali Srivastava ◽  
Rudra Deo Tripathi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heavy Metal ◽  
Heavy Metal Stress ◽  
Metal Stress

Buckwheat (Fagopyrum esculentumMoench) FeMT3 Gene in Heavy Metal Stress: Protective Role of the Protein and Inducibility of the Promoter Region under Cu2+and Cd2+Treatments

2010 ◽  
Vol 58 (6) ◽  
pp. 3488-3494 ◽  
Author(s):  
Dragana B. Nikolić ◽  
Jelena T. Samardžić ◽  
Ana M. Bratić ◽  
Ivan P. Radin ◽  
Srdjan P. Gavrilović ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Promoter Region ◽  
Heavy Metal Stress ◽  
Protective Role ◽  
Metal Stress

scholarly journals Role of Ethylene and Its Cross Talk with Other Signaling Molecules in Plant Responses to Heavy Metal Stress

2015 ◽  
Vol 169 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Nguyen Phuong Thao ◽  
M. Iqbal R. Khan ◽  
Nguyen Binh Anh Thu ◽  
Xuan Lan Thi Hoang ◽  
Mohd Asgher ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Cross Talk ◽  
Heavy Metal Stress ◽  
Signaling Molecules ◽  
Metal Stress ◽  
Plant Responses

scholarly journals Role of the Hog1 Stress-activated Protein Kinase in the Global Transcriptional Response to Stress in the Fungal PathogenCandida albicans

2006 ◽  
Vol 17 (2) ◽  
pp. 1018-1032 ◽  
Author(s):  
Brice Enjalbert ◽  
Deborah A. Smith ◽  
Michael J. Cornell ◽  
Intikhab Alam ◽  
Susan Nicholls ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heavy Metal ◽  
Protein Kinase ◽  
Transcriptional Response ◽  
Heavy Metal Stress ◽  
Transcriptional Responses ◽  
Stress Genes ◽  
The Core ◽  
Response To Stress

The resistance of Candida albicans to many stresses is dependent on the stress-activated protein kinase (SAPK) Hog1. Hence we have explored the role of Hog1 in the regulation of transcriptional responses to stress. DNA microarrays were used to characterize the global transcriptional responses of HOG1 and hog1 cells to three stress conditions that activate the Hog1 SAPK: osmotic stress, oxidative stress, and heavy metal stress. This revealed both stress-specific transcriptional responses and a core transcriptional response to stress in C. albicans. The core transcriptional response was characterized by a subset of genes that responded in a stereotypical manner to all of the stresses analyzed. Inactivation of HOG1 significantly attenuated transcriptional responses to osmotic and heavy metal stresses, but not to oxidative stress, and this was reflected in the role of Hog1 in the regulation of C. albicans core stress genes. Instead, the Cap1 transcription factor plays a key role in the oxidative stress regulation of C. albicans core stress genes. Our data show that the SAPK network in C. albicans has diverged from corresponding networks in model yeasts and that the C. albicans SAPK pathway functions in parallel with other pathways to regulate the core transcriptional response to stress.

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