scholarly journals Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics

2013 ◽  
Vol 41 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Tanecia Mitchell ◽  
Balu Chacko ◽  
Scott W. Ballinger ◽  
Shannon M. Bailey ◽  
Jianhua Zhang ◽  
...  
Keyword(s):  
Quality Control ◽  
Energy Demand ◽  
Cell Signalling ◽  
Metabolic Stress ◽  
Short Review ◽  
High Energy ◽  
Experimental Models ◽  
Signalling Pathways ◽  
Mitochondrial Quality Control ◽  
Nitrative Stress

Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic stress, such as Type II diabetes and non-alcoholic and alcoholic steatosis, the mitochondria are subjected to multiple ‘hits’ such as hypoxia and oxidative and nitrative stress, which can overwhelm the mitochondrial quality control pathways. In addition, the underlying mitochondrial genetics that evolved to accommodate high-energy demand, low-calorie supply environments may now be maladapted to modern lifestyles (low-energy demand, high-calorie environments). The pro-oxidant and pro-inflammatory environment of a sedentary western lifestyle has been associated with modified redox cell signalling pathways such as steatosis, hypoxic signalling, inflammation and fibrosis. These data suggest that loss of mitochondrial quality control is intimately associated with the aberrant activation of redox cell signalling pathways under pathological conditions. In the present short review, we discuss evidence from alcoholic liver disease supporting this concept, the insights obtained from experimental models and the application of bioenergetic-based therapeutics in the context of maintaining mitochondrial quality.

scholarly journals PINK1: A Bridge between Mitochondria and Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 371
Author(s):  
Filipa Barroso Gonçalves ◽  
Vanessa Alexandra Morais
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
High Energy ◽  
Common Denominator ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Cellular Environment ◽  
Familial Form ◽  
Mitochondrial Functions

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.

scholarly journals Impact of circadian time of dosing on cardiac-autonomous effects of glucocorticoids

2021 ◽  
Author(s):  
Michelle Wintzinger ◽  
Manoj Panta ◽  
Karen Miz ◽  
Ashok D.P. Pragasam ◽  
Michelle Sargent ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Demand ◽  
Heart Function ◽  
Daily Intake ◽  
Metabolic Stress ◽  
Single Pulse ◽  
High Energy ◽  
Dark Phase ◽  
Light Phase ◽  
Circadian Time

Bioenergetic capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates cardiac bioenergetics through the primary receptor of these drugs, the glucocorticoid receptor (GR). While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism and heart function in dystrophic mice. However, the effects of glucocorticoid intermittence on heart failure beyond muscular dystrophy remain unknown. Here we investigated the extent to which circadian time of dosing regulates the cardiac-autonomous effects of the glucocorticoid prednisone in conditions of single pulse or chronic intermittent dosing. In WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted GR ablation, and depended on an intact activating clock complex, as shown by hearts from BMAL1-KO mice. Conjugating time-of-dosing with chronic intermittence, we found that once-weekly light-phase prednisone improved metabolism and function in heart after myocardial injury. Our study identifies cardiac-autonomous mechanisms through which circadian time and chronic intermittence reconvert glucocorticoid drugs to bioenergetic boosters for the heart.

Mitophagy

2013 ◽  
Vol 55 ◽  
pp. 93-104 ◽  
Author(s):  
Thomas MacVicar
Keyword(s):  
Quality Control ◽  
High Energy ◽  
Human Diseases ◽  
Mitochondrial Network ◽  
Mitochondrial Quality Control ◽  
Selective Targeting ◽  
Autophagy Pathway ◽  
Cellular Control

Mitophagy describes the selective targeting and degradation of mitochondria by the autophagy pathway. In this process, defective mitochondria are first purged from the mitochondrial network then delivered to the lysosome by the autophagy machinery. Mitophagy has emerged as a key facet of mitochondrial quality control and has been implicated in a variety of human diseases. Disturbances in the cellular control of mitophagy can result in a dysfunctional mitochondrial network with grave implications for high energy demanding tissue. The present chapter reviews the recent advancements in the study of mitophagy mechanisms and regulation.

scholarly journals The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson’s Disease

2019 ◽  
Vol 20 (21) ◽  
pp. 5312 ◽  
Author(s):  
Kai-Jung Lin ◽  
Kai-Lieh Lin ◽  
Shang-Der Chen ◽  
Chia-Wei Liou ◽  
Yao-Chung Chuang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
Energy Demand ◽  
Neurodegenerative Disorder ◽  
High Energy ◽  
Alpha Synuclein ◽  
Special Importance ◽  
Mitochondrial Dynamic ◽  
Lysosomal System

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, mainly affecting the elderly. The disease progresses gradually, with core motor presentations and a multitude of non-motor manifestations. There are two neuropathological hallmarks of PD, the dopaminergic neuronal loss and the alpha-synuclein-containing Lewy body inclusions in the substantia nigra. While the exact pathomechanisms of PD remain unclear, genetic investigations have revealed evidence of the involvement of mitochondrial function, alpha-synuclein (α-syn) aggregation, and the endo-lysosomal system, in disease pathogenesis. Due to the high energy demand of dopaminergic neurons, mitochondria are of special importance acting as the cellular powerhouse. Mitochondrial dynamic fusion and fission, and autophagy quality control keep the mitochondrial network in a healthy state. Should defects of the organelle occur, a variety of reactions would ensue at the cellular level, including disrupted mitochondrial respiratory network and perturbed calcium homeostasis, possibly resulting in cellular death. Meanwhile, α-syn is a presynaptic protein that helps regulate synaptic vesicle transportation and endocytosis. Its misfolding into oligomeric sheets and fibrillation is toxic to the mitochondria and neurons. Increased cellular oxidative stress leads to α-syn accumulation, causing mitochondrial dysfunction. The proteasome and endo-lysosomal systems function to regulate damage and unwanted waste management within the cell while facilitating the quality control of mitochondria and α-syn. This review will analyze the biological functions and interactions between mitochondria, α-syn, and the endo-lysosomal system in the pathogenesis of PD.

scholarly journals Cardiac mitochondrial network excitability: insights from computational analysis

2012 ◽  
Vol 302 (11) ◽  
pp. H2178-H2189 ◽  
Author(s):  
Lufang Zhou ◽  
Brian O'Rourke
Keyword(s):  
Energy Demand ◽  
Computational Models ◽  
Computational Analysis ◽  
Short Review ◽  
High Energy ◽  
Mitochondrial Network ◽  
Cardiac Mitochondria ◽  
Nonlinear Network ◽  
Messenger Molecules ◽  
And Function

In the heart, mitochondria form a regular lattice and function as a coordinated, nonlinear network to continuously produce ATP to meet the high-energy demand of the cardiomyocytes. Cardiac mitochondria also exhibit properties of an excitable system: electrical or chemical signals can spread within or among cells in the syncytium. The detailed mechanisms by which signals pass among individual elements (mitochondria) across the network are still not completely understood, although emerging studies suggest that network excitability might be mediated by the local diffusion and autocatalytic release of messenger molecules such as reactive oxygen species and/or Ca2+. In this short review, we have attempted to described recent advances in the field of cardiac mitochondrial network excitability. Specifically, we have focused on how mitochondria communicate with each other through the diffusion and regeneration of messenger molecules to initiate and propagate waves or oscillations, as revealed by computational models of mitochondrial network.

scholarly journals Mitochondrial quality control and neurodegenerative diseases

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Fei Gao ◽  
Jianmin Zhang
Keyword(s):  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dynamics ◽  
High Energy ◽  
Mitochondrial Quality Control ◽  
Atp Production ◽  
Differentiated Cells ◽  
Mitochondria Dynamics ◽  
Relationship Of ◽  
High Energy Consumption

Mitochondria homeostasis is sustained by the mitochondrial quality control (MQC) system, which is crucial for cellular health, especially in the maintenance of functional mitochondria. A healthy mitochondria network is essential for life as it regulates cellular metabolism processes, particularly ATP production. Mitochondrial dynamics and mitophagy are two highly integrated processes in MQC system that determines whether damaged mitochondria will be repaired or degraded. Neurons are highly differentiated cells which demand high energy consumption. Therefore, compromised MQC processes and the accumulation of dysfunctional mitochondria may be the main cause of neuronal death and lead to neurodegeneration. Here, we focus on the inseparable relationship of mitochondria dynamics and mitophagy and how their dysfunction may lead to neurodegenerative diseases.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

scholarly journals PI3K/Akt pathway-mediated HO-1 induction regulates mitochondrial quality control and attenuates endotoxin-induced acute lung injury

2019 ◽  
Vol 99 (12) ◽  
pp. 1795-1809 ◽  
Author(s):  
Jia Shi ◽  
Jianbo Yu ◽  
Yuan Zhang ◽  
Lili Wu ◽  
Shuan Dong ◽  
...  
Keyword(s):  
Quality Control ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Akt Pathway ◽  
Mitochondrial Quality Control

scholarly journals The Quorum Sensing Auto-Inducer 2 (AI-2) Stimulates Nitrogen Fixation and Favors Ethanol Production over Biomass Accumulation in Zymomonas mobilis

2021 ◽  
Vol 22 (11) ◽  
pp. 5628
Author(s):  
Valquíria Campos Alencar ◽  
Juliana de Fátima dos Santos Silva ◽  
Renata Ozelami Vilas Boas ◽  
Vinícius Manganaro Farnézio ◽  
Yara N. L. F. de Maria ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Quorum Sensing ◽  
Ethanol Production ◽  
N2 Fixation ◽  
Energy Demand ◽  
Zymomonas Mobilis ◽  
Biomass Accumulation ◽  
High Energy ◽  
Gram Negative ◽  
Expression Of Genes

Autoinducer 2 (or AI-2) is one of the molecules used by bacteria to trigger the Quorum Sensing (QS) response, which activates expression of genes involved in a series of alternative mechanisms, when cells reach high population densities (including bioluminescence, motility, biofilm formation, stress resistance, and production of public goods, or pathogenicity factors, among others). Contrary to most autoinducers, AI-2 can induce QS responses in both Gram-negative and Gram-positive bacteria, and has been suggested to constitute a trans-specific system of bacterial communication, capable of affecting even bacteria that cannot produce this autoinducer. In this work, we demonstrate that the ethanologenic Gram-negative bacterium Zymomonas mobilis (a non-AI-2 producer) responds to exogenous AI-2 by modulating expression of genes involved in mechanisms typically associated with QS in other bacteria, such as motility, DNA repair, and nitrogen fixation. Interestingly, the metabolism of AI-2-induced Z. mobilis cells seems to favor ethanol production over biomass accumulation, probably as an adaptation to the high-energy demand of N2 fixation. This opens the possibility of employing AI-2 during the industrial production of second-generation ethanol, as a way to boost N2 fixation by these bacteria, which could reduce costs associated with the use of nitrogen-based fertilizers, without compromising ethanol production in industrial plants.

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