Daily mitochondrial dynamics in cone photoreceptors

2020 ◽  
Author(s):  
Michelle Marie Giarmarco ◽  
Daniel C Brock ◽  
Brian M Robbings ◽  
Whitney M Cleghorn ◽  
Kristine A Tsantilas ◽  
...  
Keyword(s):  
Light Exposure ◽  
Mitochondrial Dynamics ◽  
Cone Photoreceptors ◽  
Mitochondrial Structure ◽  
Energy Demands ◽  
Daily Cycles ◽  
Mitochondrial Turnover ◽  
And Function ◽  
Extracellular Structures ◽  
Daily Changes

Cone photoreceptors in the retina are exposed to intense daylight, and have higher energy demands in darkness. Cones produce energy using a large cluster of mitochondria. Mitochondria are susceptible to oxidative damage, and healthy mitochondrial populations are maintained by regular turnover. Daily cycles of light exposure and energy consumption suggest that mitochondrial turnover is important for cone health. We investigated the 3-D ultrastructure and metabolic function of zebrafish cone mitochondria throughout the day. At night cones undergo a mitochondrial biogenesis event, corresponding to an increase in the number of smaller, simpler mitochondria and increased metabolic activity. In the daytime, ER and autophagosomes associate more with mitochondria, and mitochondrial size distribution across the cluster changes. We also report dense material shared between cone mitochondria that is extruded from the cell in darkness, sometimes forming extracellular structures. Our findings reveal an elaborate set of daily changes to cone mitochondrial structure and function.

scholarly journals Daily mitochondrial dynamics in cone photoreceptors

2020 ◽  
Vol 117 (46) ◽  
pp. 28816-28827
Author(s):  
Michelle M. Giarmarco ◽  
Daniel C. Brock ◽  
Brian M. Robbings ◽  
Whitney M. Cleghorn ◽  
Kristine A. Tsantilas ◽  
...  
Keyword(s):  
Light Exposure ◽  
Mitochondrial Dynamics ◽  
Three Dimensional ◽  
Cone Photoreceptors ◽  
Energy Demands ◽  
Mitochondrial Turnover ◽  
And Function ◽  
Extracellular Structures ◽  
Endoplasmic Reticula ◽  
Daily Changes

Cone photoreceptors in the retina are exposed to intense daylight and have higher energy demands in darkness. Cones produce energy using a large cluster of mitochondria. Mitochondria are susceptible to oxidative damage, and healthy mitochondrial populations are maintained by regular turnover. Daily cycles of light exposure and energy consumption suggest that mitochondrial turnover is important for cone health. We investigated the three-dimensional (3D) ultrastructure and metabolic function of zebrafish cone mitochondria throughout the day. At night retinas undergo a mitochondrial biogenesis event, corresponding to an increase in the number of smaller, simpler mitochondria and increased metabolic activity in cones. In the daytime, endoplasmic reticula (ER) and autophagosomes associate more with mitochondria, and mitochondrial size distribution across the cluster changes. We also report dense material shared between cone mitochondria that is extruded from the cell at night, sometimes forming extracellular structures. Our findings reveal an elaborate set of daily changes to cone mitochondrial structure and function.

P5994Role of BGP-15 treatment in hypertensive heart failure progression and mitochondrial protection

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Horvath ◽  
L Deres ◽  
K Ordog ◽  
K Bruszt ◽  
B Sumegi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Function ◽  
Cardiac Remodeling ◽  
In Vitro Model ◽  
Mitochondrial Dynamics ◽  
Treated Group ◽  
Mitochondrial Structure ◽  
Vitro Model ◽  
And Function

Abstract Introduction The deterioration of mitochondrial quality control greatly contributes to the hypertension induced cardiac remodeling and progression of heart failure. Our previous in vitro results demonstrated the mitochondrial protective effect of antioxidant BGP-15 compound in the presence of cellular stress. Purpose In our recent study we investigated the effect of BGP-15 on cardiac remodeling in spontaneously hypertensive rats (SHR) with manifested heart failure and on mitochondrial dynamics and function in cell culture model. Methods 15-month-old male SHR received 25 mg/kg/day BGP-15 (SHR-B) or placebo (SHR-C) for 18 weeks. Age matched Wistar rats (WKY) were used as normotensive control. The heart function was monitored by echocardiography. Histological preparations were made from cardiac tissue. Neonatal rat cardiomyocytes (NRCMs) were used as in vitro model. 150 μM H2O2 stress and 50 μM BGP-15 treatment was applied. Mitochondrial network was stained with MitoTracker Red. Mitochondrial membrane potential was detected using JC-1 dye, while mitochondrial function was monitored by the Agilent Seahorse XFp, Cell Mito Stress Test. In both model the cellular levels of mitochondrial dynamics proteins were measured in Western blot. To study the ultrastructure we used electron microscopy in our in vivo and in vitro model. Results Left ventricular (LV) mass and LV wall thickness were increased significantly in SHR-C group compared to the initial values (p<0.05). These parameters were decreased considerably in the SHR-B group. Ejection fraction (EF%) decreased in both SHR group although this downturn was minimal because of the treatment. Chronic high blood pressure caused higher collagen deposition in SHR-C rats that was significantly diminished in the SHR-B group. Regarding the mitochondrial function decrease in the levels of fusion proteins OPA1 and MFN2 was observed in the SHR-C group. These differences were significantly reduced by BGP-15 treatment (p<0.05). Mitigation of the level of fission protein DRP1 was however reduced by BGP-15 (p<0.05). In our cellular model, we observed that the H2O2-induced mitochondrial fragmentation was decreased by BGP-15 treatment (p<0.05). BGP-15 treatment prevented mitochondrial membrane potential fall in H2O2 stress (p<0.05). There was no significant difference in basal respiration among groups by monitoring the mitochondrial function. The maximal respiration capacity and ATP production were significantly higher in the BGP-15 treated group in comparison to the stressed group (p<0.05). Conclusion BGP-15 treatment has beneficial effects on mitochondrial dynamics and structure by promoting fusion processes. It also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure. The mitigation of remodeling processes and the preserved EF in the treated group are results at least partly of the comprehensible effects of BGP-15 on mitochondrial structure and function. Acknowledgement/Funding GINOP-2.3.2-15-2016-00049; GINOP-2.3.2-15-2016-00048; GINOP-2.3.3-15-2016-00025

scholarly journals Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 286
Author(s):  
Wei-Tang Chang ◽  
Shih-Chien Huang ◽  
Hsin-Lin Cheng ◽  
Shiuan-Chih Chen ◽  
Chin-Lin Hsu
Keyword(s):  
Gallic Acid ◽  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Mitochondrial Dynamics ◽  
C2c12 Myotubes ◽  
Gene Expressions ◽  
Mitochondrial Functions ◽  
Mitochondrial Turnover ◽  
And Function

Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.

scholarly journals Effect of ApoE isoforms on mitochondria in Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 94 (23) ◽  
pp. e2404-e2411 ◽  
Author(s):  
Junxiang Yin ◽  
Eric M. Reiman ◽  
Thomas G. Beach ◽  
Geidy E. Serrano ◽  
Marwan N. Sabbagh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Human Brain ◽  
Cognitive Performance ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Structure And Function ◽  
Mitochondrial Structure ◽  
Apoe Isoforms ◽  
And Function

ObjectiveTo test the hypothesis that ApoE isoforms affect mitochondrial structure and function that are related to cognitive impairment in Alzheimer disease (AD), we systematically investigated the effects of ApoE isoforms on mitochondrial biogenesis and dynamics, oxidative stress, synapses, and cognitive performance in AD.MethodsWe obtained postmortem human brain tissues and measured proteins that are responsible for mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator-1α [PGC-1α] and sirtuin 3 [SIRT3]), for mitochondrial dynamics (mitofusin 1 [MFN1], mitofusin 2 [MFN2], and dynamin-like protein 1 [DLP1]), for oxidative stress (superoxide dismutase 2 [SOD2] and forkhead-box protein O3a [Foxo3a]), and for synapses (postsynaptic density protein 95 [PSD95] and synapsin1 [Syn1]). A total of 46 cases were enrolled, including ApoE-ɛ4 carriers (n = 21) and noncarriers (n = 25).ResultsLevels of these proteins were compared between ApoE-ɛ4 carriers and noncarriers. ApoE-ɛ4 was associated with impaired mitochondrial structure and function, oxidative stress, and synaptic integrity in the human brain. Correlation analysis revealed that mitochondrial proteins and the synaptic protein were strongly associated with cognitive performance.ConclusionApoE isoforms influence mitochondrial structure and function, which likely leads to alteration in oxidative stress, synapses, and cognitive function. These mitochondria-related proteins may be a harbinger of cognitive decline in ApoE-ɛ4 carriers and provide novel therapeutic targets for prevention and treatment of AD.

scholarly journals Heterochronic Parabiosis: Old Blood Induces Changes in Mitochondrial Structure and Function of Young Mice

2020 ◽  
Author(s):  
Jenny L Gonzalez-Armenta ◽  
Ning Li ◽  
Rae-Ling Lee ◽  
Baisong Lu ◽  
Anthony J A Molina
Keyword(s):  
Mitochondrial Respiration ◽  
Complex I ◽  
Structure And Function ◽  
Muscle Performance ◽  
Mitochondrial Morphology ◽  
Positive Effects ◽  
Mitochondrial Structure ◽  
And Function ◽  
Old Mice ◽  
Young Mice

Abstract Heterochronic parabiosis models have been utilized to demonstrate the role of blood-borne circulating factors in systemic effects of aging. In previous studies, heterochronic parabiosis has shown positive effects across multiple tissues in old mice. More recently, a study demonstrated old blood had a more profound negative effect on muscle performance and neurogenesis of young mice. In this study, we used heterochronic parabiosis to test the hypothesis that circulating factors mediate mitochondrial bioenergetic decline, a well-established biological hallmark of aging. We examined mitochondrial morphology, expression of mitochondrial complexes, and mitochondrial respiration from skeletal muscle of mice connected as heterochronic pairs, as well as young and old isochronic controls. Our results indicate that young heterochronic mice had significantly lower total mitochondrial content and on average had significantly smaller mitochondria compared to young isochronic controls. Expression of complex IV followed a similar pattern: young heterochronic mice had a trend for lower expression compared to young isochronic controls. Additionally, respirometric analyses indicate that young heterochronic mice had significantly lower complex I, complex I + II, and maximal mitochondrial respiration and a trend for lower complex II-driven respiration compared to young isochronic controls. Interestingly, we did not observe significant improvements in old heterochronic mice compared to old isochronic controls, demonstrating the profound deleterious effects of circulating factors from old mice on mitochondrial structure and function. We also found no significant differences between the young and old heterochronic mice, demonstrating that circulating factors can be a driver of age-related differences in mitochondrial structure and function.

scholarly journals Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

Oncogene ◽  
2021 ◽  
Author(s):  
Rósula García-Navas ◽  
Pilar Liceras-Boillos ◽  
Carmela Gómez ◽  
Fernando C. Baltanás ◽  
Nuria Calzada ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Redox Homeostasis ◽  
Atp Production ◽  
Oxidative Energy Metabolism ◽  
Ras Activation ◽  
Mitochondrial Defects ◽  
Critical Requirement ◽  
Dynamics And Function ◽  
And Function ◽  
And Control

AbstractSOS1 ablation causes specific defective phenotypes in MEFs including increased levels of intracellular ROS. We showed that the mitochondria-targeted antioxidant MitoTEMPO restores normal endogenous ROS levels, suggesting predominant involvement of mitochondria in generation of this defective SOS1-dependent phenotype. The absence of SOS1 caused specific alterations of mitochondrial shape, mass, and dynamics accompanied by higher percentage of dysfunctional mitochondria and lower rates of electron transport in comparison to WT or SOS2-KO counterparts. SOS1-deficient MEFs also exhibited specific alterations of respiratory complexes and their assembly into mitochondrial supercomplexes and consistently reduced rates of respiration, glycolysis, and ATP production, together with distinctive patterns of substrate preference for oxidative energy metabolism and dependence on glucose for survival. RASless cells showed defective respiratory/metabolic phenotypes reminiscent of those of SOS1-deficient MEFs, suggesting that the mitochondrial defects of these cells are mechanistically linked to the absence of SOS1-GEF activity on cellular RAS targets. Our observations provide a direct mechanistic link between SOS1 and control of cellular oxidative stress and suggest that SOS1-mediated RAS activation is required for correct mitochondrial dynamics and function.

Abstract 23: Characterization of MitoTimer, a Novel Tool for Monitoring Mitochondrial Turnover

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Christine A Thornton ◽  
Allen M Andres ◽  
Genaro Hernandez ◽  
Jon Sin ◽  
Roberta Gottlieb
Keyword(s):  
Protein Import ◽  
Spatial Information ◽  
Fluorescent Protein ◽  
Mitochondrial Dynamics ◽  
Inducible Promoter ◽  
Subcellular Fractionation ◽  
Fluorescent Reporter ◽  
Hek 293 ◽  
Mitochondrial Turnover

Fluorescent Timer, or DsRed1-E5, is a mutant of the red fluorescent protein, dsRed, developed by Terskikh and colleagues. Its fluorescence shifts over time from green to red as the protein matures. This molecular clock gives temporal and spatial information on protein turnover. To visualize mitochondrial turnover, we targeted Timer to the mitochondrial matrix with a mitochondrial targeting sequence (coined “MitoTimer”) and cloned it into a tetracycline-inducible promoter construct to regulate its expression. Here we report characterization of this novel fluorescent reporter for mitochondrial dynamics. Tet-On HEK 293 cells were transfected with pTRE-tight-MitoTimer and induced production with doxycycline. Mitochondrial distribution was demonstrated by fluorescence microscopy and verified by subcellular fractionation and western blot analysis. Doxycycline addition for as little as 1hr was sufficient to label mitochondria. MitoTimer was detected as early as 4hr following doxycycline addition, and persisted in mitochondria for at least 72hr. The color-specific conformation of MitoTimer was stable after fixation with 4% paraformaldehyde. MitoTimer matured to red fluorescence within 48hr, at which time a second pulse of doxycycline induced expression of green (immature) MitoTimer which was selectively incorporated into a subset of mitochondria actively engaged in protein import. The extent of new protein incorporation during a second pulse was increased under conditions of mito-biogenesis and reduced if mitochondrial membrane potential was dissipated. We conclude that MitoTimer can be used to monitor mitophagy and biogenesis.

Does metformin modulate mitochondrial dynamics and function in type 2 diabetic patients?

2021 ◽  
Author(s):  
Aranzazu Martinez de Marañón ◽  
Francisco Gerardo Canet ◽  
Zaida Abad-Jimenez ◽  
Ana Jover ◽  
Carlos Morillas ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Dynamics And Function ◽  
And Function ◽  
Type 2 Diabetic
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