scholarly journals Role of Mitochondria-Cytoskeleton Interactions in the Regulation of Mitochondrial Structure and Function in Cancer Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1691
Author(s):  
Jungmin Kim ◽  
Jae-Ho Cheong
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Energy Requirement ◽  
High Energy ◽  
Structure And Function ◽  
Mitochondrial Morphology ◽  
Voltage Dependent Anion Channel ◽  
Mesenchymal Transition ◽  
Mitochondrial Structure ◽  
And Function

Despite the promise of cancer medicine, major challenges currently confronting the treatment of cancer patients include chemoresistance and recurrence. The existence of subpopulations of cancer cells, known as cancer stem cells (CSCs), contributes to the failure of cancer therapies and is associated with poor clinical outcomes. Of note, one of the recently characterized features of CSCs is augmented mitochondrial function. The cytoskeleton network is essential in regulating mitochondrial morphology and rearrangement, which are inextricably linked to its functions, such as oxidative phosphorylation (OXPHOS). The interaction between the cytoskeleton and mitochondria can enable CSCs to adapt to challenging conditions, such as a lack of energy sources, and to maintain their stemness. Cytoskeleton-mediated mitochondrial trafficking and relocating to the high energy requirement region are crucial steps in epithelial-to-mesenchymal transition (EMT). In addition, the cytoskeleton itself interplays with and blocks the voltage-dependent anion channel (VDAC) to directly regulate bioenergetics. In this review, we describe the regulation of cellular bioenergetics in CSCs, focusing on the cytoskeleton-mediated dynamic control of mitochondrial structure and function.

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 Drosophila MICOS knockdown impairs mitochondrial structure and function and promotes mitophagy in muscle tissue

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio054262
Author(s):  
Li-jie Wang ◽  
Tian Hsu ◽  
Hsiang-ling Lin ◽  
Chi-yu Fu
Keyword(s):  
Muscle Tissue ◽  
Mammalian Cells ◽  
Structure And Function ◽  
Tissue Homeostasis ◽  
Mitochondrial Morphology ◽  
Mitochondrial Structure ◽  
And Function ◽  
Nucleoid Structure

ABSTRACTThe mitochondrial contact site and cristae organizing system (MICOS) is a multi-protein interaction hub that helps define mitochondrial ultrastructure. While the functional importance of MICOS is mostly characterized in yeast and mammalian cells in culture, the contributions of MICOS to tissue homeostasis in vivo remain further elucidation. In this study, we examined how knocking down expression of Drosophila MICOS genes affects mitochondrial function and muscle tissue homeostasis. We found that CG5903/MIC26-MIC27 colocalizes and functions with Mitofilin/MIC60 and QIL1/MIC13 as a Drosophila MICOS component; knocking down expression of any of these three genes predictably altered mitochondrial morphology, causing loss of cristae junctions, and disruption of cristae packing. Furthermore, the knockdown flies exhibited low mitochondrial membrane potential, fusion/fission imbalances, increased mitophagy, and limited cell death. Reductions in climbing ability indicated deficits in muscle function. Knocking down MICOS genes also caused reduced mtDNA content and fragmented mitochondrial nucleoid structure in Drosophila. Together, our data demonstrate an essential role of Drosophila MICOS in maintaining proper homeostasis of mitochondrial structure and function to promote the function of muscle tissue.

scholarly journals An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
L. Tirinato ◽  
F. Pagliari ◽  
T. Limongi ◽  
M. Marini ◽  
A. Falqui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lipid Composition ◽  
Lipid Droplets ◽  
Active Sites ◽  
Structure And Function ◽  
Key Players ◽  
And Function ◽  
And Storage ◽  
Cellular Organelles

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

Abstract 262: Knockout of Type VI Collagen Preserves Mitochondrial Structure and Function Following Myocardial Infarction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
J G Meszaros ◽  
Daniel J Luther ◽  
Patrick T Kang ◽  
Yeong-Renn Chen ◽  
R Lance Miller ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Respiratory Control ◽  
Ischemic Injury ◽  
Structure And Function ◽  
Matrix Proteins ◽  
Mitochondrial Morphology ◽  
Mitochondrial Structure ◽  
Transmission Electron ◽  
And Function

Cardiac remodeling is a dynamic process that is accelerated after myocardial infarction (MI), and the traditional focus of key extracellular matrix proteins that mediate remodeling has been on the fibrillar types I and III collagen. We have previously reported that knockout mice of the lesser-known, non-fibrillar collagen VI (Col6-/-) are protected from MI injury as evidenced by significantly reduced infarct size, fibrosis and apoptosis leading to preserved long-term cardiac function. Determining the mechanisms underlying this cardioprotection is the goal of this study. Interestingly, the Col6-/- mice are a model for Bethlam Myopathy, a rare skeletal muscular dystrophy that is characterized by mitochondrial dysfunction leading to premature apoptosis of skeletal myocytes. We hypothesized that alterations in mitochondrial structure and function in the myocardium of Col6-/- mice may play key mechanistic roles responses to ischemic injury. Mitochondrial morphology was visualized by transmission electron microscopy to compare pre- and post-MI changes. Mitochondria from uninjured Col6-/- LV tissue had similar morphology as WT, and at 3 days post-MI the mitochondrial morphology was similarly compromised in both WT and Col6-/- mice. However, at 14 days post-MI the Col6-/- mitochondria were less swollen (43 ± 5.1% decrease in overall volume) and displayed improved orientation/organization over WT (continuous strands). We measured basal O2 consumption and 24 hours post-MI in mitochondria isolated from the infarcted zones of both genotypes. The respiratory control index (RCI) of the Col6-/- mitochondria was lower in the basal, uninjured hearts (7.2 ± 0.9 in WT vs. 4.9 ± 0.6 in Col6-/-). However, the RCI of mitochondria in the infarcted region of Col6-/- hearts at 24 hours post-MI declined less than WT (post-MI values of 2.7 ± 0.5 in WT vs. 2.8 ± 0.7 in Col6-/-) . These data indicate that Col6-/- mice have preserved mitochondrial morphology and a smaller decline in respiration following MI, which may represent a novel homeostatic mechanism underlying protection from ischemic injury in the Col6-/- heart.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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