scholarly journals Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis

2018 ◽  
Vol 218 (2) ◽  
pp. 559-579 ◽  
Author(s):  
Eric M. Sawyer ◽  
Pallavi R. Joshi ◽  
Victoria Jorgensen ◽  
Julius Yunus ◽  
Luke E. Berchowitz ◽  
...  
Keyword(s):  
Cellular Differentiation ◽  
Mitochondrial Dynamics ◽  
Developmental Regulation ◽  
Cell Cortex ◽  
Mitochondrial Morphology ◽  
Cell Type ◽  
Present Evidence ◽  
Cellular Architecture ◽  
Mitochondrial Morphogenesis ◽  
Mitochondrial Remodeling

Cellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation and organelle architecture are known, but the interface between them remains unexplored. We analyzed the regulation of mitochondrial detachment from the cell cortex, a known meiotic alteration to mitochondrial morphology. We found that mitochondrial detachment is enabled by the programmed destruction of the mitochondria–endoplasmic reticulum–cortex anchor (MECA), an organelle tether that bridges mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We further present evidence for Ime2-dependent phosphorylation and degradation of MECA in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.

scholarly journals Developmental Regulation of an Organelle Tether Coordinates Mitochondrial Remodeling in Meiosis

2018 ◽  
Author(s):  
Eric M. Sawyer ◽  
Pallavi R. Joshi ◽  
Luke E. Berchowitz ◽  
Elçin Ünal
Keyword(s):  
Transcription Factor ◽  
Cellular Differentiation ◽  
Mitochondrial Dynamics ◽  
Developmental Regulation ◽  
Cell Cortex ◽  
Cell Type ◽  
Contact Sites ◽  
Cellular Architecture ◽  
Mitochondrial Morphogenesis ◽  
Mitochondrial Remodeling

ABSTRACTCellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation as well as organelle architecture are known, but the interface between them remains unexplored. We found that mitochondria abruptly detach from the cell cortex shortly before segregating into gametes. Mitochondrial detachment is enabled by the programmed destruction of the mitochondria-endoplasmic reticulum-cortex anchor (MECA), an organelle tether that forms contact sites between mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We found that MECA undergoes Ime2-dependent phosphorylation. Furthermore, Ime2 promotes MECA degradation in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.

scholarly journals Mitochondrial Dynamics in Stem Cells and Differentiation

2018 ◽  
Vol 19 (12) ◽  
pp. 3893 ◽  
Author(s):  
Bong Seo ◽  
Sang Yoon ◽  
Jeong Do
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Mitochondrial Dynamics ◽  
Cellular Reprogramming ◽  
Mitochondrial Morphology ◽  
Main Function ◽  
Tissue Formation ◽  
Atp Production

Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is adenosine triphosphate (ATP) production; however, they are additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, proliferation, differentiation, reprogramming, and aging. The change in mitochondrial morphology is closely related to the functionality of mitochondria. Normal mitochondrial dynamics are critical for cellular function, embryonic development, and tissue formation. Thus, defects in proteins involved in mitochondrial dynamics that control mitochondrial fusion and fission can affect cellular differentiation, proliferation, cellular reprogramming, and aging. Here, we review the processes and proteins involved in mitochondrial dynamics and their various associated cellular phenomena.

scholarly journals Mitochondrial Dynamics in Stem Cells and Differentiation

2018 ◽  
Author(s):  
Bong Jong Seo ◽  
Sang Hoon Yoon ◽  
Jeong Tae Do
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Development ◽  
Cellular Differentiation ◽  
Mitochondrial Dynamics ◽  
Cellular Reprogramming ◽  
Mitochondrial Morphology ◽  
Main Function ◽  
Tissue Formation ◽  
Atp Production

Mitochondria are highly dynamic organelles that continuously change their shape. Their main function is ATP production; however, they are additionally involved in a variety of cellular phenomena, such as apoptosis, cell cycle, proliferation, differentiation, reprogramming, and aging. The change in mitochondrial morphology is closely related to the functionality of mitochondria. Normal mitochondrial dynamics are critical for cellular function, embryonic development, and tissue formation. Thus, defect in proteins involved in mitochondrial dynamics that control mitochondrial fusion and fission can affect cellular differentiation, proliferation, cellular reprogramming, and aging. Here we review the processes and proteins involved in mitochondrial dynamics and its various associated cellular phenomena.

D-Fos, a target gene of Decapentaplegic signalling with a critical role during Drosophila endoderm induction

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3353-3361 ◽  
Author(s):  
J. Riese ◽  
G. Tremml ◽  
M. Bienz
Keyword(s):  
Cellular Differentiation ◽  
Target Gene ◽  
Critical Role ◽  
Cell Type ◽  
Response Factors ◽  
Present Evidence ◽  
Larval Stages ◽  
Visceral Mesoderm ◽  
Elevated Expression ◽  
Type Specification

The Drosophila endoderm is patterned by the signals Decapentaplegic and Wingless secreted from the visceral mesoderm. This induction culminates in a precise pattern of spatially restricted expression of labial, a selector gene with a role in cell type specification in the larval midgut. Here, we show that Decapentaplegic signalling induces elevated expression of the Drosophila AP-1 transcription factor D-Fos in a slightly broader endodermal region than labial. This induction occurs in parallel to, and independently of, that of labial. Furthermore, we present evidence that D-Fos is required for labial induction in the embryo as well as for maintenance of labial expression through larval stages; and that D-Fos is critical for cellular differentiation in the larval gut. We propose that Decapentaplegic, by inducing D-Fos, broadly defines an endodermal region which thus becomes predisposed to express labial, and that D-Fos cooperates with signal-activated response factors to confer the precise pattern of labial expression in this region.

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.

scholarly journals Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Anthony R. Anzell ◽  
Garrett M. Fogo ◽  
Zoya Gurm ◽  
Sarita Raghunayakula ◽  
Joseph M. Wider ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Conditional Knockout ◽  
Mitochondrial Morphology ◽  
Primary Neurons ◽  
Mitochondrial Fragmentation

AbstractMitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.

scholarly journals When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4617
Author(s):  
Styliana Kyriakoudi ◽  
Anthi Drousiotou ◽  
Petros P. Petrou
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Disease Development ◽  
Pathological Conditions ◽  
Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

scholarly journals Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Zou ◽  
Qixin Chen ◽  
Jesse Slone ◽  
Li Yang ◽  
Xiaoting Lou ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Optic Atrophy ◽  
Respiratory Function ◽  
Clinical Symptoms ◽  
Mitochondrial Dynamics ◽  
Cerebellar Atrophy ◽  
Mitochondrial Diseases ◽  
Living Cells ◽  
Mitochondrial Morphology ◽  
Mitochondrial Oxidative Phosphorylation

AbstractSLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

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