Molecular cross talk among the components of the regulatory machinery of mitochondrial structure and quality control

Cho, Hyo Min; Sun, Woong

doi:10.1038/s12276-020-0434-9

Cited by 18 publications

(7 citation statements)

References 101 publications

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“… 51 Mitophagy can accelerate mitochondrial fragmentation, which exacerbates mitochondria degradation in lysosomes and promotes muscle atrophy. 52 We also found that Flnc silencing significantly increased mitochondrial protein fragmentation, mitochondrial activity, and mitophagy, suggesting that mitophagy was activated by Flnc silencing.…”

Section: Discussionmentioning

confidence: 53%

Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy

Han¹,

Cui²,

Zhao³

et al. 2022

Molecular Therapy - Nucleic Acids

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FilaminC (Flnc) is a member of the actin binding protein family, which is preferentially expressed in the cardiac and skeletal muscle tissues. Although it is known to interact with proteins associated with myofibrillar myopathy, its unique role in skeletal muscle remains largely unknown. In this study, we identify the biological functions of Flnc in vitro and in vivo using chicken primary myoblast cells and animal models, respectively. From the results, we observe that the growth rate and mass of the skeletal muscle of fast-growing chickens (broilers) were significantly higher than those in slow-growing chickens (layers). Furthermore, we find that the expression of Flnc in the skeletal muscle of broilers was higher than that in the layers. Our results indicated that Flnc was highly expressed in the skeletal muscle, especially in the skeletal muscle of broilers than in layers. This suggests that Flnc plays a positive regulatory role in myoblast development. Flnc knockdown resulted in muscle atrophy, whereas the overexpression of Flnc promotes muscle hypertrophy in vivo in an animal model. We also found that Flnc interacted with dishevelled-2 (Dvl2), activated the wnt/β-catenin signaling pathway, and controlled skeletal muscle development. Flnc also antagonized the LC3-mediated autophagy system by decreasing Dvl2 ubiquitination. Moreover, Flnc knockdown activated and significantly increased mitophagy. In summary, these results indicate that the absence of Flnc induces autophagy or mitophagy and regulates muscle atrophy.

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Section: Discussionmentioning

confidence: 53%

Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy

Han¹,

Cui²,

Zhao³

et al. 2022

Molecular Therapy - Nucleic Acids

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“…Several in vitro and in vivo studies were performed to assess mitochondrial fission and fusion and earlier assays provided evidence that mitochondrial fission involves multiple constriction steps that are marked by the endoplasmic reticulum (ER) and dynamin-related proteins (DRPs) ( Friedman et al, 2011 ; Anand et al, 2014 ). Recent advances in light and electron microscopy demonstrated that the inner and outer membrane dynamics may be uncoupled during fission and fusion, which suggests that both processes are uniquely required to uphold the morphology of the mitochondria during its dynamic equilibrium; problems in this relationship can cause a diverse array of diseases as mitochondrial fission and fission are required for mitochondrial replication, a process critical to maintain energy levels and overall cell health ( Cho and Sun, 2020 ; Hoppins et al, 2020 ). To correctly visualize mitochondrial fusion, stable cell lines that express fluorescent mitochondrial matrices via targeted proteins must be generated; once this is done, the mitochondria can be isolated, and the fusion assay can be performed ( Hoppins et al, 2020 ).…”

Section: Assays For Studying Mitochondrial Biologymentioning

confidence: 99%

Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools

2023

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative dementia in older adults worldwide. Sadly, there are no disease-modifying therapies available for treatment due to the multifactorial complexity of the disease. AD is pathologically characterized by extracellular deposition of amyloid beta (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Increasing evidence suggest that Aβ also accumulates intracellularly, which may contribute to the pathological mitochondrial dysfunction observed in AD. According with the mitochondrial cascade hypothesis, mitochondrial dysfunction precedes clinical decline and thus targeting mitochondria may result in new therapeutic strategies. Unfortunately, the precise mechanisms connecting mitochondrial dysfunction with AD are largely unknown. In this review, we will discuss how the fruit fly Drosophila melanogaster is contributing to answer mechanistic questions in the field, from mitochondrial oxidative stress and calcium dysregulation to mitophagy and mitochondrial fusion and fission. In particular, we will highlight specific mitochondrial insults caused by Aβ and tau in transgenic flies and will also discuss a variety of genetic tools and sensors available to study mitochondrial biology in this flexible organism. Areas of opportunity and future directions will be also considered.

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“…There have, however, been hinted in the literature that the DRP1 spiral is not sufficient for the initiation of mitochondrial constrictions. Structural biology studies have revealed that the inner diameter of this multimeric ring (<200 nm) is smaller than the average diameter of a mitochondrion (~1 μm), implying the requirement for preconstriction events that precede DRP1 ring formation (Yang and Svitkina 2019;Cho and Sun 2020). The IMM constriction is thought to be a spontaneous and repetitive Constriction of Mitochondrial Inner Compartments (CoMIC), as a priming event for fission, which occurs predominantly on the IMM, independent of the OMM.…”

Section: Mitochondrial Dynamics and Its Equilibrium Mitochondrial Fis...mentioning

confidence: 99%

Mitochondrial Dynamics, Mitophagy, and Mitochondria–Endoplasmic Reticulum Contact Sites Crosstalk Under Hypoxia

Wang

Tan

Miao

et al. 2022

Front. Cell Dev. Biol.

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Mitochondria are double membrane organelles within eukaryotic cells, which act as cellular power houses, depending on the continuous availability of oxygen. Nevertheless, under hypoxia, metabolic disorders disturb the steady-state of mitochondrial network, which leads to dysfunction of mitochondria, producing a large amount of reactive oxygen species that cause further damage to cells. Compelling evidence suggests that the dysfunction of mitochondria under hypoxia is linked to a wide spectrum of human diseases, including obstructive sleep apnea, diabetes, cancer and cardiovascular disorders. The functional dichotomy of mitochondria instructs the necessity of a quality-control mechanism to ensure a requisite number of functional mitochondria that are present to fit cell needs. Mitochondrial dynamics plays a central role in monitoring the condition of mitochondrial quality. The fission–fusion cycle is regulated to attain a dynamic equilibrium under normal conditions, however, it is disrupted under hypoxia, resulting in mitochondrial fission and selective removal of impaired mitochondria by mitophagy. Current researches suggest that the molecular machinery underlying these well-orchestrated processes are coordinated at mitochondria–endoplasmic reticulum contact sites. Here, we establish a holistic understanding of how mitochondrial dynamics and mitophagy are regulated at mitochondria–endoplasmic reticulum contact sites under hypoxia.

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Molecular cross talk among the components of the regulatory machinery of mitochondrial structure and quality control

Cited by 18 publications

References 101 publications

Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy

Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy

Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools

Mitochondrial Dynamics, Mitophagy, and Mitochondria–Endoplasmic Reticulum Contact Sites Crosstalk Under Hypoxia

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