scholarly journals Mitochondria: Master Regulator of Metabolism, Homeostasis, Stress, Aging and Epigenetics

2021 ◽  
Vol 13 (3) ◽  
pp. 221-41
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Driving Force ◽  
Mitochondrial Dynamics ◽  
Cell Metabolism ◽  
Eukaryotic Cells ◽  
Cell Reprogramming ◽  
Physiological Processes ◽  
Mitochondrial Number ◽  
New Research

BACKGROUND: Mitochondria became a driving force in evolution due to their ability to manufacture adenosine triphosphate (ATP) through respiration. The functioning of mitochondria within eukaryotic cells has evolved dramatically as a result of evolution. Recent research has revealed mitochondria form plasticity to keep the cell's needs and function.CONTENT: Mitochondria have long been regarded as the cell's "powerhouse," providing energy for cell metabolism through oxidative phosphorylation (OXPHOS). A lot of physiological processes were known to be mediated by mitochondria including immunity and autophagy, cell death mechanism, and stem cell reprogramming. Mitochondria can change their shape to form a tubular network that is controlled by fission and fusion processes. Mitochondrial dynamics is the equilibrium between these two opposing processes that regulates mitochondrial number, size, and positioning within the cytoplasm.SUMMARY: All of these discoveries opened up new research avenues and revealed new targets for targeted medication development. Calorie restriction, and the mimetic agents were developed to increase mitochondria biogenesis to improve human lifespan.KEYWORDS: mitochondria, metabolism, homeostasis, stress response, aging, epigenetic

MicroRNAs in the pathogenesis of type 2 diabetes: new research progress and future direction

2018 ◽  
Vol 96 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Chenggui Miao ◽  
Guoxue Zhang ◽  
Zhongwen Xie ◽  
Jun Chang
Keyword(s):  
Cell Metabolism ◽  
Age Groups ◽  
Research Progress ◽  
Transcriptional Level ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
Elevated Glucose ◽  
Modulation Of Gene Expression ◽  
Future Direction ◽  
New Research

miRNA is a short non-coding RNA that can influence mRNA processing at the post-transcriptional level. A large number of miRNAs have been found in virtually all species so far, and these small molecules play an important role in many different physiological processes and various pathologic conditions, such as cell metabolism, cancer, autoimmune disease, and diabetes mellitus. T2D arises from a dysregulated response to the elevated glucose level in the circulation. The prevalence of T2D has increased dramatically in all age groups, and T2D in older adults is associated with more T2D complications and higher mortality. Despite the existing findings describing the pathological mechanism, T2D pathology is more complex and the pathophysiology of the disease is still not fully elucidated. In this review, we summarize the current understanding of miRNA-mediated modulation of gene expression in T2D pathogenesis, as well as related signaling pathways, and insight into the important role of miRNA in various T2D complications. Furthermore, the potential therapeutic value of miRNA for T2D patients is also discussed in detail.

scholarly journals Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility

2021 ◽  
Vol 8 ◽  
Author(s):  
Marcia Garcez ◽  
Joana Branco-Santos ◽  
Patricia C. Gracio ◽  
Catarina C. F. Homem
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Mitochondrial Dynamics ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Cell Number ◽  
Female Fertility ◽  
Mitochondrial Activity ◽  
Drosophila Ovary

The fate and proliferative capacity of stem cells have been shown to strongly depend on their metabolic state. Mitochondria are the powerhouses of the cell being responsible for energy production via oxidative phosphorylation (OxPhos) as well as for several other metabolic pathways. Mitochondrial activity strongly depends on their structural organization, with their size and shape being regulated by mitochondrial fusion and fission, a process known as mitochondrial dynamics. However, the significance of mitochondrial dynamics in the regulation of stem cell metabolism and fate remains elusive. Here, we characterize the role of mitochondria morphology in female germ stem cells (GSCs) and in their more differentiated lineage. Mitochondria are particularly important in the female GSC lineage. Not only do they provide these cells with their energy requirements to generate the oocyte but they are also the only mitochondria pool to be inherited by the offspring. We show that the undifferentiated GSCs predominantly have fissed mitochondria, whereas more differentiated germ cells have more fused mitochondria. By reducing the levels of mitochondrial dynamics regulators, we show that both fused and fissed mitochondria are required for the maintenance of a stable GSC pool. Surprisingly, we found that disrupting mitochondrial dynamics in the germline also strongly affects nurse cells morphology, impairing egg chamber development and female fertility. Interestingly, reducing the levels of key enzymes in the Tricarboxylic Acid Cycle (TCA), known to cause OxPhos reduction, also affects GSC number. This defect in GSC self-renewal capacity indicates that at least basal levels of TCA/OxPhos are required in GSCs. Our findings show that mitochondrial dynamics is essential for female GSC maintenance and female fertility, and that mitochondria fusion and fission events are dynamically regulated during GSC differentiation, possibly to modulate their metabolic profile.

scholarly journals Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic mountain sickness

2018 ◽  
Vol 125 (3) ◽  
pp. 832-840 ◽  
Author(s):  
Helen Zhao ◽  
Guy Perkins ◽  
Hang Yao ◽  
David Callacondo ◽  
Otto Appenzeller ◽  
...  
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Mitochondrial Dynamics ◽  
Induced Pluripotent Stem Cell ◽  
Mitochondrial Morphology ◽  
Chronic Mountain Sickness ◽  
Atp Levels ◽  
Mountain Sickness ◽  
Induced Pluripotent

Patients with chronic mountain sickness (CMS) suffer from hypoxemia, erythrocytosis, and numerous neurologic deficits. Here we used induced pluripotent stem cell (iPSC)-derived neurons from both CMS and non-CMS subjects to study CMS neuropathology. Using transmission electron microscopy, we report that CMS neurons have a decreased mitochondrial volume density, length, and less cristae membrane surface area. Real-time PCR confirmed a decreased mitochondrial fusion gene optic atrophy 1 (OPA1) expression. Immunoblot analysis showed an accumulation of the short isoform of OPA1 (S-OPA1) in CMS neurons, which have reduced ATP levels under normoxia and increased lactate dehydrogenase (LDH) release and caspase 3 activation after hypoxia. Improving the balance between the long isoform of OPA1 and S-OPA1 in CMS neurons increased the ATP levels and attenuated LDH release under hypoxia. Our data provide initial evidence for altered mitochondrial morphology and function in CMS neurons, and reveal increased cell death under hypoxia due in part to altered mitochondrial dynamics. NEW & NOTEWORTHY Induced pluripotent stem cell-derived neurons from chronic mountain sickness (CMS) subjects have altered mitochondrial morphology and dynamics, and increased sensitivity to hypoxic stress. Modification of OPA1 can attenuate cell death after hypoxic treatment, providing evidence that altered mitochondrial dynamics play an important role in increased vulnerability under stress in CMS neurons.

scholarly journals Plant Mitophagy in Comparison to Mammals: What Is Still Missing?

2021 ◽  
Vol 22 (3) ◽  
pp. 1236
Author(s):  
Kaike Ren ◽  
Lanlan Feng ◽  
Shuangli Sun ◽  
Xiaohong Zhuang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Plant Cells ◽  
Molecular Evidence ◽  
Double Membrane ◽  
Mitochondrial Homeostasis ◽  
A Cell ◽  
Mitochondrial Number

Mitochondrial homeostasis refers to the balance of mitochondrial number and quality in a cell. It is maintained by mitochondrial biogenesis, mitochondrial fusion/fission, and the clearance of unwanted/damaged mitochondria. Mitophagy represents a selective form of autophagy by sequestration of the potentially harmful mitochondrial materials into a double-membrane autophagosome, thus preventing the release of death inducers, which can trigger programmed cell death (PCD). Recent advances have also unveiled a close interconnection between mitophagy and mitochondrial dynamics, as well as PCD in both mammalian and plant cells. In this review, we will summarize and discuss recent findings on the interplay between mitophagy and mitochondrial dynamics, with a focus on the molecular evidence for mitophagy crosstalk with mitochondrial dynamics and PCD.

Abstract 463: Circadian Clock Disruption Promotes Cardiac Cell Death During Hypoxic Injury

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Lorrie A Kirshenbaum ◽  
Inna Rabinovich ◽  
Tami A Martino
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Circadian Rhythms ◽  
Cardiac Myocytes ◽  
Cell Metabolism ◽  
Loss Of Function ◽  
Hypoxic Injury ◽  
Physiological Processes ◽  
Signaling Axis ◽  
Turn Over

Circadian rhythms play a fundamental role in cell metabolism and tissue homeostasis as well as in the diurnal oscillation of physiological processes such as blood pressure. Zeitgebers influence the circadian rhythms by serving as molecular switches for re-setting the intrinsic cellular clock. Herein, we show that oxygen is a Zeitgeber for the circadian rhythm and regulator of clock gene expression in cardiac myocytes. We further show that clock gene regulation promotes survival of cardiac myocytes by a mechanism that bi-directionally influences mitochondrial clearance and autophagy. Cardiac myocytes exhibited phasic oscillations in clock gene expression under basal conditions which was disrupted during hypoxia. This was accompanied by a marked time dependent decline in clock gene transcription that was maximal at ZT+18 and coincided with a reciprocal increase in mitochondrial clearance. Loss of function mutations of clock that disrupted nuclear localization or DNA binding to BMAL-1 promoted wide-spread cell death. Hence, the findings of the present study provide a novel signaling axis that operationally links hypoxia regulated clock gene expression and mitochondrial turn-over to cell survival.

scholarly journals Altered Mitochondrial Dynamics Contributes to Propofol-induced Cell Death in Human Stem Cell–derived Neurons

2015 ◽  
Vol 123 (5) ◽  
pp. 1067-1083 ◽  
Author(s):  
Danielle M. Twaroski ◽  
Yasheng Yan ◽  
Ivan Zaja ◽  
Eric Clark ◽  
Zeljko J. Bosnjak ◽  
...  
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Embryonic Stem ◽  
Treated Group ◽  
Cyclin Dependent Kinase ◽  
Related Protein

Abstract Background Studies in developing animals have shown that anesthetic agents can lead to neuronal cell death and learning disabilities when administered early in life. Development of human embryonic stem cell–derived neurons has provided a valuable tool for understanding the effects of anesthetics on developing human neurons. Unbalanced mitochondrial fusion and fission lead to various pathological conditions including neurodegeneration. The aim of this study was to dissect the role of mitochondrial dynamics in propofol-induced neurotoxicity. Methods Terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate in situ nick-end labeling staining was used to assess cell death in human embryonic stem cell–derived neurons. Mitochondrial fission was assessed using TOM20 staining and electron microscopy. Expression of mitochondrial fission-related proteins was assessed by Western blot, and confocal microscopy was used to assess opening time of the mitochondrial permeability transition pore (mPTP). Results Exposure to 6 h of 20 μg/ml propofol increased cell death from 3.18 ± 0.17% in the control-treated group to 9.6 ± 0.95% and led to detrimental increases in mitochondrial fission (n = 5 coverslips per group) accompanied by increased expression of activated dynamin-related protein 1 and cyclin-dependent kinase 1, key proteins responsible for mitochondrial fission. Propofol exposure also induced earlier opening of the mPTP from 118.9 ± 3.1 s in the control-treated group to 73.3 ± 1.6 s. Pretreatment of the cells with mdivi-1, a mitochondrial fission blocker rescued the propofol-induced toxicity, mitochondrial fission, and mPTP opening time (n = 75 cells per group). Inhibiting cyclin-dependent kinase 1 attenuated the increase in cell death and fission and the increase in expression of activated dynamin-related protein 1. Conclusion These data demonstrate for the first time that propofol-induced neurotoxicity occurs through a mitochondrial fission/mPTP-mediated pathway.

scholarly journals Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging

2017 ◽  
Vol 216 (8) ◽  
pp. 2315-2327 ◽  
Author(s):  
Christopher L. Koehler ◽  
Guy A. Perkins ◽  
Mark H. Ellisman ◽  
D. Leanne Jones
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mitochondrial Dynamics ◽  
Cell Metabolism ◽  
Functional Decline ◽  
Cell Activity ◽  
Cellular Tissue ◽  
Tissue Homeostasis ◽  
Age Related

Intestinal stem cells (ISCs) maintain the midgut epithelium in Drosophila melanogaster. Proper cellular turnover and tissue function rely on tightly regulated rates of ISC division and appropriate differentiation of daughter cells. However, aging and epithelial injury cause elevated ISC proliferation and decreased capacity for terminal differentiation of daughter enteroblasts (EBs). The mechanisms causing functional decline of stem cells with age remain elusive; however, recent findings suggest that stem cell metabolism plays an important role in the regulation of stem cell activity. Here, we investigate how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference–mediated knockdown of factors involved in mitochondrial dynamics. ISC/EB-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced ISC proliferation, in part, through induction of ISC senescence. Our results indicate an uncoupling of cellular, tissue, and organismal aging through inhibition of ISC proliferation and provide insight into strategies used by stem cells to maintain tissue homeostasis despite severe damage to organelles.

The early development of antenna and antennal sensilla in the noctuid moth, Agrotis segetum (Insecta: Lepidoptera)

1990 ◽  
Vol 48 (3) ◽  
pp. 502-503
Author(s):  
Eric Hallberg ◽  
Lina Hansén
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Early Development ◽  
Larval Stage ◽  
Pupal Stage ◽  
Agrotis Segetum ◽  
Antennal Sensilla ◽  
Noctuid Moth ◽  
Standard Procedures

The antennal rudiments in lepidopterous insects are present as disks during the larval stage. The tubular double-walled antennal disk is present beneath the larval antenna, and its inner layer gives rise to the adult antenna during the pupal stage. The sensilla develop from a cluster of cells that are derived from one stem cell, which gives rise to both sensory and enveloping cells. During the morphogenesis of the sensillum these cells undergo major transformations, including cell death. In the moth Agrotis segetum the pupal stage lasts about 14 days (temperature, 25°C). The antennae, clearly seen from the exterior, were dissected and fixed according to standard procedures (3 % glutaraldehyde in 0.15 M cacaodylate buffer, followed by 1 % osmiumtetroxide in the same buffer). Pupae from day 1 to day 8, of both sexes were studied.

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