It takes two to tango: The essential role of ER-mitochondrial contact sites in mitochondrial dynamics

Hemel, Irene M.G.M.; Sarantidou, Rita; Gerards, Mike

doi:10.1016/j.biocel.2021.106101

Cited by 9 publications

(10 citation statements)

References 31 publications

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“…The proteolytic processing of L-OPA1 leads to the accumulation of S-OPA1, which binds to the Mic60 subunit of the MICOS complex, preventing the outer-inner membrane tethering, and thus contributing to the IMM constriction (Figure 5B) (Cho et al, 2017). Although CoMIC does not appear to be able to completely sever the IMM, it induces the transient dissociation of the OMM-IMM contact (Figure 5B) (Cho et al, 2017;Chakrabarti et al, 2018;Hemel et al, 2021). In addition, recent studies have shown that mitochondria undergoing CoMIC have a higher probability of subsequent mitochondrial fission, furthermore, mitochondrial fission occurs at the foci of CoMIC, and conditions blocking CoMIC can also inhibit fission of mitochondria (Cho et al, 2017;Chakrabarti et al, 2018).…”

Section: Multiple Constriction Events Of the Inner And Outer Mitochon...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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Section: Multiple Constriction Events Of the Inner And Outer Mitochon...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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“…The preservation of the overall mitochondrial network morphology and integrity relies on the balance between mitochondrial fusion and fission processes known as mitochondrial dynamics; its coordination cycles with finely tuned mitochondrial turnover are regulated by biogenesis and mitophagy (Romanello and Sandri, 2022). Mitochondrial fusion is the process where mitochondria merge and aid in stress alleviation by diluting components of partially impaired mitochondria (Hemel et al, 2021;Wang et al, 2022). Fusion is mediated by the outer mitochondrial membrane-bound GTPases, Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2), and the optic atrophy protein 1 (OPA1), a dynamin-like GTPase in charge of the inner membrane fusion (Romanello and Sandri, 2022).…”

Section: Bidirectional Regulation Between Mitochondrial Dynamics and ...mentioning

confidence: 99%

“…Fission is mediated by DRP1 and its adaptor proteins such as the mitochondrial fission factor (Mff), the mitochondrial fission one protein (Fis1), and the mitochondrial elongation factor 2/ mitochondrial dynamics protein 49 (MIEF2/MiD49 and MIEF/ 1/MiD 51). Fission is a process that promotes the separation and segregation of dysfunctional mitochondria for selective elimination (Hemel et al, 2021;Romanello and Sandri, 2022;Wang et al, 2022). Mitochondrial dynamics is one of the fundamental ways in which cells achieve control over the population and function of their mitochondria under stress conditions, allowing mitochondria to respond and accommodate immediately to cellular stress (Wang et al, 2022).…”

Section: Bidirectional Regulation Between Mitochondrial Dynamics and ...mentioning

confidence: 99%

“…Mitochondrial dynamics is one of the fundamental ways in which cells achieve control over the population and function of their mitochondria under stress conditions, allowing mitochondria to respond and accommodate immediately to cellular stress (Wang et al, 2022). Current research suggests that the molecular machinery underlying the well-orchestrated processes of mitochondrial fusion and fission are coordinated at MAMs (Hemel et al, 2021;Wang et al, 2022). Mfn1 and Mfn2 can be localized in mitochondria, particularly in punctate structures where ER tubules cross the mitochondrial membrane-forming nodes.…”

Section: Bidirectional Regulation Between Mitochondrial Dynamics and ...mentioning

confidence: 99%

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Role of mitochondria-associated endoplasmic reticulum membranes in insulin sensitivity, energy metabolism, and contraction of skeletal muscle

Nieblas

Pérez-Treviño²,

Garcı́a³

2022

Front. Mol. Biosci.

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Skeletal muscle has a critical role in the regulation of the energy balance of the organism, particularly as the principal tissue responsible for insulin-stimulated glucose disposal and as the major site of peripheral insulin resistance (IR), which has been related to accumulation of lipid intermediates, reduced oxidative capacity of mitochondria and endoplasmic reticulum (ER) stress. These organelles form contact sites, known as mitochondria-associated ER membranes (MAMs). This interconnection seems to be involved in various cellular processes, including Ca2+ transport and energy metabolism; therefore, MAMs could play an important role in maintaining cellular homeostasis. Evidence suggests that alterations in MAMs may contribute to IR. However, the evidence does not refer to a specific subcellular location, which is of interest due to the fact that skeletal muscle is constituted by oxidative and glycolytic fibers as well as different mitochondrial populations that appear to respond differently to stimuli and pathological conditions. In this review, we show the available evidence of possible differential responses in the formation of MAMs in skeletal muscle as well as its role in insulin signaling and the beneficial effect it could have in the regulation of energetic metabolism and muscular contraction.

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“…It has been shown that SelN also colocalizes with Mitochondria Associated Membranes (MAMs) that tether the mitochondria to the ER (Filipe et al, 2021). MAMs allow for Ca 2+ influx from the ER into the mitochondria, phospholipid synthesis and transport, regulation of mitochondrial dynamics, among other vital cell functions (Hemel et al, 2021; Nieblas et al, 2022). Based on these findings, we hypothesize that mitochondria dysregulation may play a vital role in the disease mechanism of SELENON -RM.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish and cellular models ofSELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes

Barraza-Flores,

Moghadaszadeh,

Lee

et al. 2024

Preprint

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SELENON-Related Myopathy (SELENON-RM) is a rare congenital myopathy caused by mutations of theSELENONgene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology commonly includes multiminicores or a dystrophic pattern but is often non-specific. TheSELENONgene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency causesSELENON-RM are undetermined. A hurdle is the lack of cellular and animal models that show assayable phenotypes. Here we report deep-phenotyping of SelN-deficient zebrafish and muscle cells. SelN-deficient zebrafish exhibit changes in embryonic muscle function and swimming activity in larvae. Analysis of single cell RNAseq data in a zebrafish embryo-atlas revealed coexpression betweenselenonand genes involved in glutathione redox pathway. SelN-deficient zebrafish and mouse myoblasts exhibit changes in glutathione and redox homeostasis, suggesting a direct relationship with SelN function. We report changes in metabolic function abnormalities in SelN-null myotubes when compared to WT. These results suggest that SelN has functional roles during zebrafish early development and myoblast metabolism.

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It takes two to tango: The essential role of ER-mitochondrial contact sites in mitochondrial dynamics

Cited by 9 publications

References 31 publications

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

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

Role of mitochondria-associated endoplasmic reticulum membranes in insulin sensitivity, energy metabolism, and contraction of skeletal muscle

Zebrafish and cellular models ofSELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes

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