scholarly journals Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane-Induced Cell Toxicity

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ming Li ◽  
Jiguang Guo ◽  
Hongjie Wang ◽  
Yuzhen Li
Keyword(s):  
Pediatric Surgery ◽  
Cell Function ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Pathway ◽  
Cell Toxicity ◽  
Mitochondrial Homeostasis ◽  
Unpleasant Odor ◽  
Inhalational Anesthetic ◽  
Indispensable Tool ◽  
The Stability

General anesthesia is a powerful and indispensable tool to ensure the accomplishment of surgical procedures or clinical examinations. Sevoflurane as an inhalational anesthetic without unpleasant odor is commonly used in clinical practice, especially for pediatric surgery. However, the toxicity caused by sevoflurane has gained growing attention. Mitochondria play a key role in maintaining cellular metabolism and survival. To maintain the stability of mitochondrial homeostasis, they are constantly going through fusion and fission. Also, damaged mitochondria need to be degraded by autophagy, termed as mitophagy. Accumulating evidence proves that sevoflurane exposure in young age could lead to cell toxicity by triggering the mitochondrial pathway of apoptosis, inducing the abnormalities of mitochondrial dynamics and mitophagy. In the present review, we focus on the current understanding of mitochondrial apoptosis, dynamics and mitophagy in cell function, the implications for cell toxicity in response to sevoflurane, and their underlying potential mechanisms.

scholarly journals Inhibition of Mitochondrial Dynamics Preferentially Targets Pancreatic Cancer Cells with Enhanced Tumorigenic and Invasive Potential

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 698
Author(s):  
Sarah Courtois ◽  
Beatriz de Luxán-Delgado ◽  
Laure Penin-Peyta ◽  
Alba Royo-García ◽  
Beatriz Parejo-Alonso ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Metastatic Potential ◽  
Ductal Adenocarcinoma ◽  
Expression Ratio ◽  
Cytotoxic Effects ◽  
Mitochondrial Homeostasis ◽  
Pancreatic Cancer Cells ◽  
Tumorigenic Potential ◽  
Dose Dependent

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, partly due to its intrinsic aggressiveness, metastatic potential, and chemoresistance of the contained cancer stem cells (CSCs). Pancreatic CSCs strongly rely on mitochondrial metabolism to maintain their stemness, therefore representing a putative target for their elimination. Since mitochondrial homeostasis depends on the tightly controlled balance between fusion and fission processes, namely mitochondrial dynamics, we aim to study this mechanism in the context of stemness. In human PDAC tissues, the mitochondrial fission gene DNM1L (DRP1) was overexpressed and positively correlated with the stemness signature. Moreover, we observe that primary human CSCs display smaller mitochondria and a higher DRP1/MFN2 expression ratio, indicating the activation of the mitochondrial fission. Interestingly, treatment with the DRP1 inhibitor mDivi-1 induced dose-dependent apoptosis, especially in CD133+ CSCs, due to the accumulation of dysfunctional mitochondria and the subsequent energy crisis in this subpopulation. Mechanistically, mDivi-1 inhibited stemness-related features, such as self-renewal, tumorigenicity, and invasiveness and chemosensitized the cells to the cytotoxic effects of Gemcitabine. In summary, mitochondrial fission is an essential process for pancreatic CSCs and represents an attractive target for designing novel multimodal treatments that will more efficiently eliminate cells with high tumorigenic potential.

scholarly journals Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 238 ◽  
Author(s):  
Blanca Hernando-Rodríguez ◽  
Marta Artal-Sanz
Keyword(s):  
Quality Control ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Stress Responses ◽  
Membrane Lipids ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Gene ◽  
Control Mechanisms ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Functions

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress, and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the oxidative phosphorylation (OXPHOS) system for ATP production. It requires, in addition, the import of a large number of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue, and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPRmt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial prohibitin (PHB) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

scholarly journals Unraveling the Impact of Cysteine-to-Serine Mutations on the Structural and Functional Properties of Cu(I)-Binding Proteins

2019 ◽  
Vol 20 (14) ◽  
pp. 3462 ◽  
Author(s):  
Pavlin ◽  
Qasem ◽  
Sameach ◽  
Gevorkyan-Airapetov ◽  
Ritacco ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Cell Function ◽  
Working Mechanism ◽  
Essential Requirement ◽  
Aggregation Propensity ◽  
Structural And Functional Properties ◽  
Stability Structure ◽  
The Stability ◽  
The Impact ◽  
Partner Proteins

Appropriate maintenance of Cu(I) homeostasis is an essential requirement for proper cell function because its misregulation induces the onset of major human diseases and mortality. For this reason, several research efforts have been devoted to dissecting the inner working mechanism of Cu(I)-binding proteins and transporters. A commonly adopted strategy relies on mutations of cysteine residues, for which Cu(I) has an exquisite complementarity, to serines. Nevertheless, in spite of the similarity between these two amino acids, the structural and functional impact of serine mutations on Cu(I)-binding biomolecules remains unclear. Here, we applied various biochemical and biophysical methods, together with all-atom simulations, to investigate the effect of these mutations on the stability, structure, and aggregation propensity of Cu(I)-binding proteins, as well as their interaction with specific partner proteins. Among Cu(I)-binding biomolecules, we focused on the eukaryotic Atox1-ATP7B system, and the prokaryotic CueR metalloregulator. Our results reveal that proteins containing cysteine-to-serine mutations can still bind Cu(I) ions; however, this alters their stability and aggregation propensity. These results contribute to deciphering the critical biological principles underlying the regulatory mechanism of the in-cell Cu(I) concentration, and provide a basis for interpreting future studies that will take advantage of cysteine-to-serine mutations in Cu(I)-binding systems.

scholarly journals Protective Effects of Euthyroidism Restoration on Mitochondria Function and Quality Control in Cardiac Pathophysiology

2019 ◽  
Vol 20 (14) ◽  
pp. 3377 ◽  
Author(s):  
Francesca Forini ◽  
Giuseppina Nicolini ◽  
Claudia Kusmic ◽  
Giorgio Iervasi
Keyword(s):  
Quality Control ◽  
Cell Function ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Disease Onset ◽  
Cell Loss ◽  
Protective Effects ◽  
Mitochondrial Homeostasis ◽  
Cardiac Pathophysiology ◽  
Adverse Remodeling

Mitochondrial dysfunctions are major contributors to heart disease onset and progression. Under ischemic injuries or cardiac overload, mitochondrial-derived oxidative stress, Ca2+ dis-homeostasis, and inflammation initiate cross-talking vicious cycles leading to defects of mitochondrial DNA, lipids, and proteins, concurrently resulting in fatal energy crisis and cell loss. Blunting such noxious stimuli and preserving mitochondrial homeostasis are essential to cell survival. In this context, mitochondrial quality control (MQC) represents an expanding research topic and therapeutic target in the field of cardiac physiology. MQC is a multi-tier surveillance system operating at the protein, organelle, and cell level to repair or eliminate damaged mitochondrial components and replace them by biogenesis. Novel evidence highlights the critical role of thyroid hormones (TH) in regulating multiple aspects of MQC, resulting in increased organelle turnover, improved mitochondrial bioenergetics, and the retention of cell function. In the present review, these emerging protective effects are discussed in the context of cardiac ischemia-reperfusion (IR) and heart failure, focusing on MQC as a strategy to blunt the propagation of connected dangerous signaling cascades and limit adverse remodeling. A better understanding of such TH-dependent signaling could provide insights into the development of mitochondria-targeted treatments in patients with cardiac disease.

scholarly journals Recurrent nonsevere hypoglycemia exacerbates imbalance of mitochondrial homeostasis leading to synapse injury and cognitive deficit in diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. E973-E986 ◽  
Author(s):  
Yu Zhou ◽  
Lishan Huang ◽  
Wenting Zheng ◽  
Jingjing An ◽  
Zhidong Zhan ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Mitochondrial Dynamics ◽  
Morris Water Maze Test ◽  
Interacting Protein ◽  
Mitochondrial Energy Metabolism ◽  
Mitochondrial Homeostasis ◽  
Chronic Hyperglycemia ◽  
Marker Proteins ◽  
Patients With Diabetes ◽  
Adenovirus E1b

Recurrent nonsevere hypoglycemia (RH) can lead to cognitive dysfunction in patients with diabetes, although the involved mechanisms remain unclear. Here, we aimed to investigate the mechanism underlying RH-induced cognitive deficits with a focus on mitochondrial homeostasis. To establish a model that mimicked RH in patients with type 1 diabetes (T1DM) receiving insulin therapy, streptozotocin-induced mice with T1DM were subjected to recurrent, twice-weekly insulin injections over 4 wk. We found that RH disrupted the mitochondrial fine structure, reduced the number of mitochondria, and upregulated the expression of mitochondrial dynamics and mitophagy markers, including dynamin-related protein 1 (Drp1), Bcl-2/adenovirus E1B 19-kDa-interacting protein-3 (BNIP3), and microtubule-associated protein 1 light-chain 3 (LC3) in the hippocampus of T1DM mice. Moreover, RH and chronic hyperglycemia synergistically promoted the production of reactive oxygen species, impaired mitochondrial membrane potential, and suppressed mitochondrial energy metabolism. Under diabetic conditions, RH also altered the synaptic morphology and reduced the expression of synaptic marker proteins. Long-term recognition memory and spatial memory, assessed with the Morris water maze test, were also impaired. However, these effects were largely prevented by mitochondrial division inhibitor 1, a potent and selective Drp1 inhibitor. Thus, it appears that RH exacerbates the imbalance of mitochondrial homeostasis, leading to synapse injury and cognitive deficits in diabetes. The adjustment of mitochondrial homeostasis could serve as an effective neuroprotective approach when addressing low blood sugar conditions.

scholarly journals Lymphotoxin: stimulation and regulation of colony-stimulating factors in fibroblasts

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2383-2390
Author(s):  
M Akashi ◽  
M Saito ◽  
HP Koeffler
Keyword(s):  
Cell Function ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Activated Lymphocytes ◽  
Colony Stimulating Factors ◽  
Gm Csf ◽  
Csf Proteins ◽  
Consensus Region ◽  
The Stability ◽  
And Function

Colony-stimulating factors (CSFs) are pivotal for proliferation and function of hematopoietic cells. We found that lymphotoxin, a product of activated lymphocytes, stimulates accumulation of granulocyte- macrophage (GM)-CSF and macrophage (M)-CSF proteins and mRNAs in fibroblasts. An increase in GM- and M-CSF mRNA levels occurred within 2 hours after addition of 1,000 U/mL lymphotoxin and levels plateaued over the next 24 hours. Tumor necrosis factor alpha (TNF alpha) was about five times more potent than lymphotoxin at low concentrations, and was nearly 1.5 to to 2 times more potent at maximally stimulating concentrations of the cytokines. Stimulation by lymphotoxin did not require either new protein synthesis or protein kinase-C stimulation. Stability studies of GM- and M-CSF transcripts in fibroblasts showed that M-CSF mRNA was five times more stable (half-life [t 1/2], 100 minutes) than GM-CSF mRNA (t 1/2, 20 minutes). Stability of these mRNAs was unchanged after stimulation of the cells with lymphotoxin. In addition, exposure of cells to 12-O-tetradecanoylphorbol 13-acetate did not alter stability of M-CSF mRNA but markedly prolonged the stability of GM-CSF mRNA. This is consistent with data showing that the AT-rich consensus region in the 3′ untranslated region of many transiently expressed cytokines including GM-CSF but not M-CSF, play a major role in their mRNA stability. Our results suggest that activated lymphocytes can affect hematopoietic cell function and growth by stimulating production of CSFs by mesenchymal cells.

scholarly journals Role of GTPase-Dependent Mitochondrial Dynamins in Heart Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiangen Liu ◽  
Xianjing Song ◽  
Youyou Yan ◽  
Bin Liu
Keyword(s):  
Cell Function ◽  
Morphological Changes ◽  
Heart Function ◽  
Mitochondrial Dynamics ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Dependent Manner

Heart function maintenance requires a large amount of energy, which is supplied by the mitochondria. In addition to providing energy to cardiomyocytes, mitochondria also play an important role in maintaining cell function and homeostasis. Although adult cardiomyocyte mitochondria appear as independent, low-static organelles, morphological changes have been observed in cardiomyocyte mitochondria under stress or pathological conditions. Indeed, cardiac mitochondrial fission and fusion are involved in the occurrence and development of heart diseases. As mitochondrial fission and fusion are primarily regulated by mitochondrial dynamins in a GTPase-dependent manner, GTPase-dependent mitochondrial fusion (MFN1, MFN2, and OPA1) and fission (DRP1) proteins, which are abundant in the adult heart, can also be regulated in heart diseases. In fact, these dynamic proteins have been shown to play important roles in specific diseases, including ischemia-reperfusion injury, heart failure, and metabolic cardiomyopathy. This article reviews the role of GTPase-dependent mitochondrial fusion and fission protein-mediated mitochondrial dynamics in the occurrence and development of heart diseases.

scholarly journals SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Princz ◽  
Federico Pelisch ◽  
Nektarios Tavernarakis
Keyword(s):  
Caenorhabditis Elegans ◽  
Posttranslational Modifications ◽  
Stress Resistance ◽  
Important Determinant ◽  
Mitochondrial Dynamics ◽  
C Elegans ◽  
Mitochondrial Homeostasis ◽  
Somatic Tissues ◽  
Transcription Regulators ◽  
Influence Gene Expression

Abstract The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. Here, we show that ageing elicits a marked increase of SUMO levels in C. elegans. In turn, SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. SUMOylation of DAF-16 modulates mitochondrial homeostasis by interfering with mitochondrial dynamics and mitophagy. Our findings reveal that SUMO is an important determinant of lifespan, and provide novel insight, relevant to the complexity of the signalling mechanisms that influence gene expression to govern organismal survival in metazoans.

scholarly journals Lymphotoxin: stimulation and regulation of colony-stimulating factors in fibroblasts

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2383-2390 ◽  
Author(s):  
M Akashi ◽  
M Saito ◽  
HP Koeffler
Keyword(s):  
Cell Function ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Activated Lymphocytes ◽  
Colony Stimulating Factors ◽  
Gm Csf ◽  
Csf Proteins ◽  
Consensus Region ◽  
The Stability ◽  
And Function

Abstract Colony-stimulating factors (CSFs) are pivotal for proliferation and function of hematopoietic cells. We found that lymphotoxin, a product of activated lymphocytes, stimulates accumulation of granulocyte- macrophage (GM)-CSF and macrophage (M)-CSF proteins and mRNAs in fibroblasts. An increase in GM- and M-CSF mRNA levels occurred within 2 hours after addition of 1,000 U/mL lymphotoxin and levels plateaued over the next 24 hours. Tumor necrosis factor alpha (TNF alpha) was about five times more potent than lymphotoxin at low concentrations, and was nearly 1.5 to to 2 times more potent at maximally stimulating concentrations of the cytokines. Stimulation by lymphotoxin did not require either new protein synthesis or protein kinase-C stimulation. Stability studies of GM- and M-CSF transcripts in fibroblasts showed that M-CSF mRNA was five times more stable (half-life [t 1/2], 100 minutes) than GM-CSF mRNA (t 1/2, 20 minutes). Stability of these mRNAs was unchanged after stimulation of the cells with lymphotoxin. In addition, exposure of cells to 12-O-tetradecanoylphorbol 13-acetate did not alter stability of M-CSF mRNA but markedly prolonged the stability of GM-CSF mRNA. This is consistent with data showing that the AT-rich consensus region in the 3′ untranslated region of many transiently expressed cytokines including GM-CSF but not M-CSF, play a major role in their mRNA stability. Our results suggest that activated lymphocytes can affect hematopoietic cell function and growth by stimulating production of CSFs by mesenchymal cells.

Encrypted Genes and Their Assembly in Ciliates

2004 ◽  
Author(s):  
David M. Prescott ◽  
Grzegorz Rozenberg
Keyword(s):  
Life Cycle ◽  
Normal Cell ◽  
Cell Function ◽  
Gene Evolution ◽  
Gene Density ◽  
Somatic Nucleus ◽  
New Genes ◽  
Species Survival ◽  
The Stability ◽  
Spacer Dna

Maintenance of normal cell function and structure requires some level of stability of the cell’s DNA—at least the DNA that makes up the genes of the cell. In most eukaryotes most of the DNA in the genome does not encode genes and has no known function beyond forming long spacers between successive genes. For example, the gene density in the germline (micronuclear) genome of stichotrich ciliates (formerly referred to as hypotrich ciliates) is very low; only a few percent of the DNA encodes the approximately 27,000 different genes, and more than 95% is spacer DNA. Powerful DNA repair systems guard the stability both of nongene and gene DNA in contemporary cells, protecting it against mutagenesis. Although species survival depends on DNA stability, cell evolution requires changes in DNA. Presumably, there is a balance between instability of DNA that allows evolution and a stability that protects species from mutational extinction. Could cells evolve strategies that change the balance, allowing a greater rate of DNA change (gene evolution) without jeopardizing species survival? The stichotrichs may, in fact, have evolved such a mechanism, dramatically modifying their germline DNA during evolution to facilitate creation of new genes without reducing the level of cell survival. The modifications of germline DNA in ciliates, in turn, require dramatic DNA processing to convert germline DNA into somatic DNA during the life cycle of the organisms. The ciliate strategy rests on the evolution of nuclear dimorphism: the inclusion both of a germline nucleus (micronucleus) and a somatic nucleus (macronucleus) in the same cell (Figure 9.1; for a general review, see Prescott [6, 7]). Like the example in Figure 9.1, most stichotrich species contain two or more micronuclei and two or more macronuclei per cell. The multiple micronuclei are genetically identical to each other, and the multiple macronuclei are genetically identical; these multiplicities of nuclei have no bearing on the issues addressed in this chapter. The micronucleus is used only in cell mating, and its genes are silent. Hence, micronuclear genes do not support the maintenance, growth, or division of the cell.

Sign in / Sign up

Export Citation Format

Share Document