Stat2-Drp1 mediated mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages

Distribution of mitochondria as well as other intracellular organelles in mammalian cells is regulated by interphase microtubules. Here, we demonstrate a role of microtubules in the mitochondrial biogenesis using various microtubule-active drugs and human osteosarcoma cell line 143B cells and rat liver-derived RL-34 cells. Depolymerization of microtubules by nocodazole or colchicine, as well as 2-methoxyestradiol, a natural estrogen metabolite, arrested asynchronously cultured cells in G(2)/M phase of cell cycle and at the same time inhibited the mitochondrial mass increase and mtDNA replication. These drugs also inhibited the mitochondrial mass increase in the cells that were synchronized in cell cycle, which should occur during G(1) to G(2) phase progression in normal conditions. However, stabilization of microtubules by taxol did not affect the proliferation of mitochondria during the cell cycle, yet a prolonged incubation of cells with taxol induced an abnormal accumulation of mitochondria in cells arrested in G(2)/M phase of cell cycle. Taxol-induced accumulation of mitochondria was not only demonstrated by mitochondria-specific fluorescent dyes but also evidenced by the examination of cells transfected with yellow fluorescent protein fused with mitochondrial targeting sequence from subunit VIII of human cytochrome c oxidase (pEYFP) and by enhanced mtDNA replication. Two subpopulations of mitochondria were detected in taxol-treated cells: mitochondria with high Delta(psi)(m), detectable either by Mito Tracker Red CMXRos or by Green FM, and those with low Delta(psi)(m), detectable only by Green FM. However, taxol-induced increases in the mitochondrial mass and in the level of acetylated (alpha)-tubulin were abrogated by a co-treatment with taxol and nocodazole or taxol and colchicine. These data strongly suggest that interphase microtubules may be essential for the regulation of mitochondrial biogenesis in mammalian cells.

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Corrigendum to ‘Stat2-Drp1 mediated mitochondrial mass increase is necessary for pro-inflammatory differentiation of macrophages’[Redox Biology 37 (2020) 101761]

Redox Biology ◽

10.1016/j.redox.2020.101786 ◽

2020 ◽

pp. 101786

Author(s):

Weihua Yu ◽

Xin Wang ◽

Jiuzhou Zhao ◽

Rui Liu ◽

Jiangzheng Liu ◽

...

Keyword(s):

Mitochondrial Mass ◽

Redox Biology ◽

Mass Increase

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Mitochondrial mass and function is regulated by PI3K signaling in thyroid cancer cells

Endocrine Abstracts ◽

10.1530/endoabs.32.oc3.2 ◽

2013 ◽

Author(s):

K Alexander Iwen ◽

Erich Schroder ◽

Julia Resch ◽

Ulrich Lindner ◽

Peter Konig ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Pi3k Signaling ◽

Mitochondrial Mass ◽

And Function ◽

Thyroid Cancer Cells

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Ethephon for American Ginseng (Panax quiquefolium L.) Inflorescence Removal

HortScience ◽

10.21273/hortsci.33.3.481b ◽

1998 ◽

Vol 33 (3) ◽

pp. 481b-481

Author(s):

A.E. Fiebig ◽

J.T.A. Proctor ◽

D. Murr ◽

R. Releeder

Keyword(s):

Additive Concentration ◽

Root Mass ◽

Panax Quinquefolium ◽

Fruit Removal ◽

Plant Damage ◽

Low Concentrations ◽

Production Practice ◽

Whole Plants ◽

Mass Increase ◽

Standard Production

Varying concentrations (500-4000 mg·L–1) of ethephon, an ethylene-releasing compound, were applied to 3-year-old ginseng (Panax quinquefolium L.) plants in fields of southern Ontario. The effects of this chemical on fruit removal, plant damage, infructescence morphology, and root mass were studied and compared to the normal practice of manual inflorescence removal. The highest concentrations had the highest rates of removal but also caused the greatest amount of damage to the whole plants when compared to the mid-range concentrations. The lowest concentrations showed less foliar damage but did not provide sufficient fruit removal to mimic hand removal. When individual inflorescences of the ethephon treatments were studied, the seed heads had fewer ripe berries and more unpollinated florets than the untreated controls. When root masses were compared, high and low concentrations showed lower masses than those of the standard production practice of hand removal. However, mid range concentrations showed similar root mass increase to manual removal. When all parameters were considered, the concentration range giving the best results was 1000-1500 mg·L–1. Multiple applications of ethephon, at weekly intervals, had an additive effect on flower removal and plant damage. Treatments having an additive concentration of over 2000 mg·L–1 had detrimental effects on all parameters. Those within the 1000–1500 mg·L–1 range showed the highest similarity to the hand removal benefits.

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A 1-Month Ketogenic Diet Increased Mitochondrial Mass in Red Gastrocnemius Muscle, but not in the Brain or Liver of Middle-Aged Mice

Nutrients ◽

10.3390/nu13082533 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2533

Author(s):

Zeyu Zhou ◽

Jocelyn Vidales ◽

José A González-Reyes ◽

Bradley Shibata ◽

Keith Baar ◽

...

Keyword(s):

Prefrontal Cortex ◽

Gastrocnemius Muscle ◽

Left Lobe ◽

Middle Aged ◽

Mitochondrial Content ◽

Mitochondrial Mass ◽

Aged Mice ◽

Fractional Area ◽

Ketogenic Diets ◽

The Impact

Alterations in markers of mitochondrial content with ketogenic diets (KD) have been reported in tissues of rodents, but morphological quantification of mitochondrial mass using transmission electron microscopy (TEM), the gold standard for mitochondrial quantification, is needed to further validate these findings and look at specific regions of interest within a tissue. In this study, red gastrocnemius muscle, the prefrontal cortex, the hippocampus, and the liver left lobe were used to investigate the impact of a 1-month KD on mitochondrial content in healthy middle-aged mice. The results showed that in red gastrocnemius muscle, the fractional area of both subsarcolemmal (SSM) and intermyofibrillar (IMM) mitochondria was increased, and this was driven by an increase in the number of mitochondria. Mitochondrial fractional area or number was not altered in the liver, prefrontal cortex, or hippocampus following 1 month of a KD. These results demonstrate tissue-specific changes in mitochondrial mass with a short-term KD and highlight the need to study different muscle groups or tissue regions with TEM to thoroughly determine the effects of a KD on mitochondrial mass.

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GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage

Nature Communications ◽

10.1038/s41467-021-23715-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Lauren A. Callender ◽

Johannes Schroth ◽

Elizabeth C. Carroll ◽

Conor Garrod-Ketchley ◽

Lisa E. L. Romano ◽

...

Keyword(s):

Dna Damage ◽

T Cells ◽

T Cell ◽

Mitochondrial Biogenesis ◽

Cell Manipulation ◽

Th2 Cells ◽

Related Factor ◽

Mitochondrial Mass ◽

T Helper 2 ◽

And Function

AbstractGATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4+ T cell viability and function after DNA damage.

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Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy

Biology ◽

10.3390/biology10050349 ◽

2021 ◽

Vol 10 (5) ◽

pp. 349

Author(s):

Rodrigo Prieto-Carrasco ◽

Fernando E. García-Arroyo ◽

Omar Emiliano Aparicio-Trejo ◽

Pedro Rojas-Morales ◽

Juan Carlos León-Contreras ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Mitochondrial Biogenesis ◽

Renal Mass ◽

Renal Damage ◽

Peroxisome Proliferator ◽

Progressive Reduction ◽

Ckd Progression ◽

Peroxisome Proliferator Activated Receptor ◽

Mitochondrial Mass ◽

Mitochondrial Impairment

The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.

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