scholarly journals Double-edge sword roles of iron in driving energy production versus instigating ferroptosis

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuping Zhang ◽  
Wei Xin ◽  
Gregory J. Anderson ◽  
Ruibin Li ◽  
Ling Gao ◽  
...  
Keyword(s):  
Fenton Reaction ◽  
Energy Production ◽  
Iron Homeostasis ◽  
Regulated Cell Death ◽  
Double Edge ◽  
Double Edge Sword ◽  
Novel Interactions ◽  
Metabolic Activities ◽  
Species Production

AbstractIron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

scholarly journals Double Edge Sword: The Role of Neutrophils in Tuberculosis

10.5772/31324 ◽  
2012 ◽  
Author(s):  
Patricia Gonzlez-Cano ◽  
Rommel Chacn-Salinas ◽  
Victoria Ramos-Kichik ◽  
Rogelio Hernndez-Pando ◽  
Jeanet Serafn-Lpez ◽  
...  
Keyword(s):  
Double Edge ◽  
Double Edge Sword

scholarly journals Iron Metabolism in Obesity and Metabolic Syndrome

2020 ◽  
Vol 21 (15) ◽  
pp. 5529
Author(s):  
Álvaro González-Domínguez ◽  
Francisco M. Visiedo-García ◽  
Jesús Domínguez-Riscart ◽  
Raúl González-Domínguez ◽  
Rosa M. Mateos ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Iron Metabolism ◽  
Fenton Reaction ◽  
Iron Homeostasis ◽  
Living Organism ◽  
Nutritional Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Pathological Conditions

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

scholarly journals The role of autophagy in the pathogenesis of ischemic stroke

2020 ◽  
Vol 18 ◽  
Author(s):  
Qianyu Shi ◽  
Quancheng Cheng ◽  
Chunhua Chen
Keyword(s):  
Ischemic Stroke ◽  
Physiological Condition ◽  
Exact Role ◽  
Double Edge ◽  
Double Edge Sword ◽  
Autophagy Pathway ◽  
Underlying Mechanisms ◽  
And Function ◽  
Glucose Supply

: Autophagy is a strictly regulated process which degrades and recycles long-lived or misfolded proteins and damaged organelles for the maintenance of energy and function homeostasis of cells. Insufficient oxygen and glucose supply caused by cerebral ischemia leads to higher ratio of AMP/ATP, which will activate AMPK pathway to initiate the process of autophagy. Accumulating evidence shows that autophagy participates in the pathogenesis of ischemic stroke as a doubleedge sword. However, the exact role of autophagy in the pathogenesis of ischemic stroke is controversial and yet to be elucidated. In this review, we expounded the autophagy pathway both in physiological condition and in ischemic stroke. We also focused on discussing the double-edge sword effect of autophagy in brain ischemia and its underlying mechanisms. In addition, we reviewed potential therapeutic strategies for ischemic stroke targeting autophagy pathway.

scholarly journals The Double Edge Sword of Testosterone’s Role in the COVID-19 Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Johnny S. Younis ◽  
Karl Skorecki ◽  
Zaid Abassi
Keyword(s):  
Human Body ◽  
Complex Disease ◽  
Normal Male ◽  
Disease Development ◽  
Age Related ◽  
Double Edge ◽  
Double Edge Sword ◽  
Health And Disease ◽  
High Level

COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve. In this mini-review, we focus on the role of testosterone through a discussion of the intricate mechanisms of disease development and deterioration. Accumulated evidence suggests that there are links between high level (normal male level) as well as low level (age-related hypogonadism) testosterone in disease progression and expansion, supporting its role as a double-edged sword. Unresolved questions point to the essential need for further targeted studies to substantiate these contrasting mechanisms.

scholarly journals Engineered Genetic Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes

2018 ◽  
Author(s):  
Silvia Ambrós ◽  
Francisca De la Iglesia ◽  
Sttefany M. Rosario ◽  
Anamarija Butković ◽  
Santiago F. Elena
Keyword(s):  
Viral Rna ◽  
Deleterious Mutations ◽  
Genetic Redundancy ◽  
Compensatory Evolution ◽  
Double Edge ◽  
Double Edge Sword ◽  
Evolution Experiment ◽  
Endogenous Genes ◽  
The One

1AbstractGenetic redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here we tackle the role of genetic redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppression of RNA silencing plant defense, of tobacco etch potyvirus (TEV). TEV genotypes containing deleterious mutations in presence/absence of engineered genetic redundancy were evolved and the pattern of fitness and virulence recovery evaluated. Genetically redundant genotypes suffered less from the effect of deleterious mutations and showed relatively minor changes in fitness and virulence. By contrast, non-genetically redundant genotypes had very low fitness and virulence at the beginning of the evolution experiment that were fully recovered by the end. At the molecular level, the outcome depended on the combination of the actual mutations being compensated and the presence/absence of genetic redundancy. Reversions to wild-type alleles were the norm in the non-redundant genotypes while redundant ones either did not fix any mutation at all or showed a higher nonsynonymous mutational load.

scholarly journals The Role of Apoptosis as a Double-Edge Sword in Cancer

2021 ◽  
Author(s):  
Reyhaneh Farghadani ◽  
Rakesh Naidu
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Master Regulators ◽  
Double Edge ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Double Edge Sword ◽  
Apoptotic Pathways

The pathogenesis of many diseases is most closely related to inappropriate apoptosis (either too little or too much) and cancer is one of the situations where too little apoptosis happens, leading to malignant cells that highly proliferate. Defects at any points along apoptotic pathways may lead to malignant transformation of the affected cells, tumor metastasis, and resistance to anti-cancer drugs. Several major molecular mechanisms are involved in the evasion of apoptosis in cancer initiation and progression. Bcl-2 family of proteins and caspases are the central players in the apoptotic mechanism and regulate cell death. Their imperfections cause to the deficient apoptotic signaling and thereby the inadequate apoptosis in cancer cells and eventually carcinogenesis. Strategies targeting these master regulators in carcinoma cells has been a major focus of interest in cancer studies. Therefore, despite being the cause of problem, apoptosis can be targeted in cancer therapy. This chapter provides a comprehensive review of apoptotic cell death and how deficiencies in apoptotic master regulators, caspases and Bcl-2 family proteins, influence carcinogenesis and can be targeted in cancer treatment.

The role of autophagy in pulmonary hypertension: a double-edge sword

APOPTOSIS ◽  
2018 ◽  
Vol 23 (9-10) ◽  
pp. 459-469 ◽  
Author(s):  
Rui Chen ◽  
Meiping Jiang ◽  
Bo Li ◽  
Wei Zhong ◽  
Zhongqun Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Double Edge ◽  
Double Edge Sword

scholarly journals Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Min Lim ◽  
Ezanee Azlina Mohamad Hanif ◽  
Siok-Fong Chin
Keyword(s):  
Cancer Therapeutics ◽  
Tumour Microenvironment ◽  
Disease Stage ◽  
Hormonal Stimulation ◽  
Double Edge ◽  
Essential Components ◽  
Double Edge Sword ◽  
Context Specific ◽  
External Stimuli

AbstractAutophagy is a conserved cellular process required to maintain homeostasis. The hallmark of autophagy is the formation of a phagophore that engulfs cytosolic materials for degradation and recycling to synthesize essential components. Basal autophagy is constitutively active under normal conditions and it could be further induced by physiological stimuli such as hypoxia, nutrient starvation, endoplasmic reticulum stress,energy depletion, hormonal stimulation and pharmacological treatment. In cancer, autophagy is highly context-specific depending on the cell type, tumour microenvironment, disease stage and external stimuli. Recently, the emerging role of autophagy as a double-edged sword in cancer has gained much attention. On one hand, autophagy suppresses malignant transformation by limiting the production of reactive oxygen species and DNA damage during tumour development. Subsequently, autophagy evolved to support the survival of cancer cells and promotes the tumourigenicity of cancer stem cells at established sites. Hence, autophagy is an attractive target for cancer therapeutics and researchers have been exploiting the use of autophagy modulators as adjuvant therapy. In this review, we present a summary of autophagy mechanism and controlling pathways, with emphasis on the dual-role of autophagy (double-edged sword) in cancer. This is followed by an overview of the autophagy modulation for cancer treatment and is concluded by a discussion on the current perspectives and future outlook of autophagy exploitation for precision medicine.

Sign in / Sign up

Export Citation Format

Share Document