scholarly journals Mitochondrial Dynamics in Adult Cardiomyocytes and Heart Diseases

2020 ◽  
Vol 8 ◽  
Author(s):  
Anqi Li ◽  
Meng Gao ◽  
Wenting Jiang ◽  
Yuan Qin ◽  
Guohua Gong
Keyword(s):  
Mitochondrial Dynamics ◽  
Heart Diseases ◽  
Cell Types ◽  
Oxidative Stress Response ◽  
Mitochondrial Morphology ◽  
Cellular Functions ◽  
Mature Adult ◽  
Adult Cardiomyocytes ◽  
Atp Generation ◽  
The Relationship

Mitochondria are the powerhouse organelles of cells; they participate in ATP generation, calcium homeostasis, oxidative stress response, and apoptosis. Thus, maintenance of mitochondrial function is critical for cellular functions. As highly dynamic organelles, the function of mitochondria is dynamically regulated by their fusion and fission in many cell types, which regulate mitochondrial morphology, number, distribution, metabolism, and biogenesis in cells. Mature rod-shaped cardiomyocytes contain thousands of end-to-end contacted spheroid mitochondria. The movement of mitochondria in these cells is limited, which hinders the impetus for research into mitochondrial dynamics in adult cardiomyocytes. In this review, we discuss the most recent progress in mitochondrial dynamics in mature (adult) cardiomyocytes and the relationship thereof with heart diseases.

scholarly journals Mitochondrial Biogenesis, Mitochondrial Dynamics, and Mitophagy in the Maturation of Cardiomyocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2463
Author(s):  
Qianqian Ding ◽  
Yanxiang Qi ◽  
Suk-Ying Tsang
Keyword(s):  
Stem Cells ◽  
Mitochondrial Biogenesis ◽  
Pluripotent Stem Cells ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
The Other ◽  
Cellular Functions ◽  
Self Renewal ◽  
Mitochondrial Mass ◽  
Excellent Source

Pluripotent stem cells (PSCs) can undergo unlimited self-renewal and can differentiate into all the cell types present in our body, including cardiomyocytes. Therefore, PSCs can be an excellent source of cardiomyocytes for future regenerative medicine and medical research studies. However, cardiomyocytes obtained from PSC differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. In this review, we aim to summarize previous findings on the changes of mitochondrial biogenesis, mitophagy, and mitochondrial dynamics during the maturation of cardiomyocytes. In addition, we intend to summarize whether changes in these processes would affect the maturation of cardiomyocytes. Lastly, we aim to discuss unanswered questions in the field and to provide insights for the possible strategies of enhancing the maturation of PSC-derived cardiomyocytes.

scholarly journals CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology

2008 ◽  
Vol 182 (3) ◽  
pp. 573-585 ◽  
Author(s):  
Xiao-Jian Han ◽  
Yun-Fei Lu ◽  
Shun-Ai Li ◽  
Taku Kaitsuka ◽  
Yasufumi Sato ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Time Lapse ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
Voltage Dependent ◽  
Dependent Protein ◽  
Time Lapse Imaging

Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types.

scholarly journals An analysis of respiratory function and mitochondrial morphology in Candida albicans

2019 ◽  
Author(s):  
Lucian Duvenage ◽  
Daniel R. Pentland ◽  
Carol A. Munro ◽  
Campbell W. Gourlay
Keyword(s):  
Candida Albicans ◽  
Respiratory Function ◽  
Fungal Pathogens ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Mitochondrial Activity ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Response To Stress ◽  
And Oxidative Stress

AbstractRespiratory function and mitochondrial dynamics have been well characterised in a number of cell types, including the model yeast Saccharomyces cerevisiae, but remain under-researched in fungal pathogens such as Candida albicans. An understanding of mitochondrial activity and morphology is important if we are to understand the role that this organelle plays in adaption and response to stress. Here we examine the respiratory profiles of several prominent pathogenic Candida species and present a useful GFP probe for the study of mitochondrial morphology. We examine mitochondrial morphology under a variety of conditions that Candida species may encounter within the host, such as acidic pH, respiratory and oxidative stress. The GFP probe also allowed for the visualisation of mitochondria during hyphal development, during growth following macrophage engulfment and distribution within biofilms. These data demonstrate that the mitochondrial network of C. albicans is highly responsive to both environmental conditions and developmental cues, suggesting important roles for this organelle in environmental adaption.

scholarly journals Changes in Drp1 Function and Mitochondrial Morphology Are Associated with the α-Synuclein Pathology in a Transgenic Mouse Model of Parkinson’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 885
Author(s):  
Philipp Portz ◽  
Michael K. Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Transgene Expression ◽  
Mitochondrial Dynamics ◽  
Transgenic Mouse Model ◽  
Mitochondrial Morphology ◽  
Pathological Changes ◽  
The Relationship

Alterations in mitochondrial function and morphology are associated with many human diseases, including cancer and neurodegenerative diseases. Mitochondrial impairment is linked to Parkinson’s disease (PD) pathogenesis, and alterations in mitochondrial dynamics are seen in PD models. In particular, α-synuclein (αS) abnormalities are often associated with pathological changes to mitochondria. However, the relationship between αS pathology and mitochondrial dynamics remains poorly defined. Herein, we examined a mouse model of α-synucleinopathy for αS pathology-linked alterations in mitochondrial dynamics in vivo. We show that α-synucleinopathy in a transgenic (Tg) mouse model expressing familial PD-linked mutant A53T human αS (TgA53T) is associated with a decrease in Drp1 localization and activity in the mitochondria. In addition, we show that the loss of Drp1 function in the mitochondria is associated with two distinct phenotypes of enlarged neuronal mitochondria. Mitochondrial enlargement was only present in diseased animals and, apart from Drp1, other proteins involved in mitochondrial dynamics are unlikely to cause these changes, as their levels remained mostly unchanged. Further, the levels of Mfn1, a protein that facilitates mitochondrial fusion, was decreased nonspecifically with transgene expression. These results support the view that altered mitochondrial dynamics are a significant neuropathological factor in α-synucleinopathies.

scholarly journals Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts

2013 ◽  
Vol 305 (12) ◽  
pp. H1736-H1751 ◽  
Author(s):  
Jin O-Uchi ◽  
Bong Sook Jhun ◽  
Stephen Hurst ◽  
Sara Bisetto ◽  
Polina Gross ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Cardiac Cells ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Atp Production ◽  
H9c2 Myoblasts

Ca+ influx to mitochondria is an important trigger for both mitochondrial dynamics and ATP generation in various cell types, including cardiac cells. Mitochondrial Ca2+ influx is mainly mediated by the mitochondrial Ca2+ uniporter (MCU). Growing evidence also indicates that mitochondrial Ca2+ influx mechanisms are regulated not solely by MCU but also by multiple channels/transporters. We have previously reported that skeletal muscle-type ryanodine receptor (RyR) type 1 (RyR1), which expressed at the mitochondrial inner membrane, serves as an additional Ca2+ uptake pathway in cardiomyocytes. However, it is still unclear which mitochondrial Ca2+ influx mechanism is the dominant regulator of mitochondrial morphology/dynamics and energetics in cardiomyocytes. To investigate the role of mitochondrial RyR1 in the regulation of mitochondrial morphology/function in cardiac cells, RyR1 was transiently or stably overexpressed in cardiac H9c2 myoblasts. We found that overexpressed RyR1 was partially localized in mitochondria as observed using both immunoblots of mitochondrial fractionation and confocal microscopy, whereas RyR2, the main RyR isoform in the cardiac sarcoplasmic reticulum, did not show any expression at mitochondria. Interestingly, overexpression of RyR1 but not MCU or RyR2 resulted in mitochondrial fragmentation. These fragmented mitochondria showed bigger and sustained mitochondrial Ca2+ transients compared with basal tubular mitochondria. In addition, RyR1-overexpressing cells had a higher mitochondrial ATP concentration under basal conditions and showed more ATP production in response to cytosolic Ca2+ elevation compared with nontransfected cells as observed by a matrix-targeted ATP biosensor. These results indicate that RyR1 possesses a mitochondrial targeting/retention signal and modulates mitochondrial morphology and Ca2+-induced ATP production in cardiac H9c2 myoblasts.

The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease

2016 ◽  
Vol 130 (21) ◽  
pp. 1861-1874 ◽  
Author(s):  
Kathleen Atkins ◽  
Asish Dasgupta ◽  
Kuang-Hueih Chen ◽  
Jeff Mewburn ◽  
Stephen L. Archer
Keyword(s):  
Cell Proliferation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Adaptor Proteins ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
Disease States

Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM). This review focuses on Drp1 adaptor proteins that also regulate fission. The proteins include fission 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial dynamics proteins of 49 kDa and 51 kDa (MiD49, MiD51). Heterologous MiD overexpression sequesters inactive Drp1 on the OMM, promoting fusion; conversely, increased endogenous MiD creates focused Drp1 multimers that optimize OMM scission. The triggers that activate MiD-bound Drp1 in disease states are unknown; however, MiD51 has a unique capacity for ADP binding at its nucleotidyltransferase domain. Without ADP, MiD51 inhibits Drp1, whereas ADP promotes MiD51-mediated fission, suggesting a link between metabolism and fission. Confusion over whether MiDs mediate fusion (by sequestering inactive Drp1) or fission (by guiding Drp1 assembly) relates to a failure to consider cell types used and to distinguish endogenous compared with heterologous changes in expression. We speculate that endogenous MiDs serve as Drp1-binding partners that are dysregulated in disease states and may be important targets for inhibiting cell proliferation and ischemia/reperfusion injury. Moreover, it appears that the composition of the fission apparatus varies between disease states and amongst individuals. MiDs may be important targets for inhibiting cell proliferation and attenuating ischemia/reperfusion injury.

scholarly journals Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons

2021 ◽  
Vol 13 ◽  
Author(s):  
Sandra Lizbeth Morales-Rosales ◽  
Roberto Santín-Márquez ◽  
Pedro Posadas-Rodriguez ◽  
Ruth Rincon-Heredia ◽  
Teresa Montiel ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cortical Neurons ◽  
Redox State ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
Premature Senescence ◽  
Neuronal Viability

The decline in brain function during aging is one of the most critical health problems nowadays. Although senescent astrocytes have been found in old-age brains and neurodegenerative diseases, their impact on the function of other cerebral cell types is unknown. The aim of this study was to evaluate the effect of senescent astrocytes on the mitochondrial function of a neuron. In order to evaluate neuronal susceptibility to a long and constant senescence-associated secretory phenotype (SASP) exposure, we developed a model by using cellular cocultures in transwell plates. Rat primary cortical astrocytes were seeded in transwell inserts and induced to premature senescence with hydrogen peroxide [stress-induced premature senescence (SIPS)]. Independently, primary rat cortical neurons were seeded at the bottom of transwells. After neuronal 6 days in vitro (DIV), the inserts with SIPS-astrocytes were placed in the chamber and cocultured with neurons for 6 more days. The neuronal viability, the redox state [reduced glutathione/oxidized glutathione (GSH/GSSG)], the mitochondrial morphology, and the proteins and membrane potential were determined. Our results showed that the neuronal mitochondria functionality was altered after being cocultured with senescent astrocytes. In vivo, we found that old animals had diminished mitochondrial oxidative phosphorylation (OXPHOS) proteins, redox state, and senescence markers as compared to young rats, suggesting effects of the senescent astrocytes similar to the ones we observed in vitro. Overall, these results indicate that the microenvironment generated by senescent astrocytes can affect neuronal mitochondria and physiology.

Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure

2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang
Keyword(s):  
Heart Failure ◽  
Particulate Matter ◽  
Inflammatory Response ◽  
Heart Diseases ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Inflammatory Mechanism ◽  
High Concentrations ◽  
Future Work ◽  
The Relationship

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.

scholarly journals Machine learning-based classification of mitochondrial morphology in primary neurons and brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Garrett M. Fogo ◽  
Anthony R. Anzell ◽  
Kathleen J. Maheras ◽  
Sarita Raghunayakula ◽  
Joseph M. Wider ◽  
...  
Keyword(s):  
Image Analysis ◽  
Cortical Neurons ◽  
Mitochondrial Dynamics ◽  
Automated Image Analysis ◽  
Mitochondrial Morphology ◽  
Analysis Pipeline ◽  
Genetic Ablation ◽  
Block Face

AbstractThe mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.

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