Stress-induced hyperacetylation of microtubule enhances mitochondrial fission and modulates the phosphorylation of Drp1 at 616Ser

Perdiz, Daniel; Lorin, Séverine; Leroy-Gori, Ingrid; Poüs, Christian

doi:10.1016/j.cellsig.2017.07.020

Cited by 42 publications

(23 citation statements)

References 46 publications

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“…Additionally, the decrease in F-actin occurred in parallel with an accumulation of G-actin ( Fig. 4E and G), an end-product of F-actin depolymerization (48), suggesting that mitochondrial fission stimulated the dissociation and disrupted the synthesis of F-actin. Mdivi1 reduced the conversion of F-actin to G-actin.…”

Section: Zea Impairs Esc Migration Via the Activation Of Mitochondriamentioning

confidence: 87%

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

Wang

Zhao

et al. 2018

Mol Med Report

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Increased endometrial stromal cell (ESC) survival and migration is responsible for the development and progression of endometriosis. However, little is known about the mechanisms underlying ESC survival and migration, and limited therapeutic strategies that are able to reverse these abnormalities are available. The present study investigated the effects of zearalenone (ZEA) on ESC survival and migration, particularly focusing on mitochondrial fission and the c‑Jun N‑terminal kinase (JNK)/dynamin‑related protein 1 (Drp1) pathway. The results revealed that ZEA induced ESC apoptosis in a dose‑dependent manner. Furthermore, ZEA treatment triggered excessive mitochondrial fission resulting in structural and functional mitochondrial damage, leading to the collapse of the mitochondrial membrane potential and subsequent leakage of cytochrome c into the cytoplasm. This triggered the mitochondrial pathway of apoptosis. Additionally, ZEA‑induced mitochondrial fission decreased ESC migration through F‑actin/G‑actin homeostasis dysregulation. ZEA also increased JNK phosphorylation and subsequently Drp1 phosphorylation at the serine 616 position, resulting in Drp1 activation. JNK/Drp1 pathway inhibition abolished the inhibitory effects of ZEA on ESC survival and migration. In summary, the present study demonstrated that ZEA reduced ESC survival and migration through the stimulation of mitochondrial fission by activation of the JNK/Drp1 pathway.

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Section: Zea Impairs Esc Migration Via the Activation Of Mitochondriamentioning

confidence: 87%

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

Wang

Zhao

et al. 2018

Mol Med Report

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“…Western blot analysis of Ptbp2 cKO testis lysates revealed elevated levels of DRP1, a critical regulator of mitochondrial fission. While DRP1-mediated fission can be regulated by post-translational modifications (Kashatus et al, 2015;Kim et al, 2016;Perdiz et al, 2017), over-expression of DRP1 alone can result in increased mitochondrial fission (Fowler and O'Sullivan, 2016;Ma et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

PTBP2-dependent alternative splicing regulates protein transport and mitochondria morphology in post-meiotic germ cells.

Hannigan

Fujioka

Brett-Morris

et al. 2018

Preprint

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The RNA binding protein PTBP2 (polypyrimidine tract binding protein 2) is a key regulator of tissue-specific alternative RNA splicing. In the testis, PTBP2 is expressed in meiotic and post-meiotic germ cells (spermatocytes and spermatids, respectively). In these cells, PTBP2 is required for proper alternative mRNA splicing for over 200 genes, disproportionately affecting genes encoding proteins involved in protein trafficking via transport vesicles. In this study, we used electron microscopy to test the hypothesis that protein trafficking is impaired in the absence of PTBP2, and to further investigate why spermatogenesis abruptly ceases in PTBP2-deficienct spermatids. Ultrastructural analysis shows that protein trafficking in spermatids is aberrant in the absence of PTBP2. Unexpectedly, we also found that mitochondria morphology and number are significantly altered in PTBP2-deficient spermatids, consistent with increased mitochondria fission. Furthermore, we show that genes with key roles in mitochondria dynamics and function are post-transcriptionally regulated by PTBP2 and in different stages of spermatogenesis. Collectively, the data provide ultrastructural evidence that alternative splicing regulation by PTBP2 during spermatogenesis is critical for proper regulation of protein trafficking and mitochondria morphology.

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“…Much of our understanding of motor‐protein‐based transport comes from the study of mitochondrial motility in neurons, where long‐range transport is thought to be mediated by interactions of mitochondria with microtubule based motors (Saxton & Hollenbeck, ; Schwarz, ). There is a growing body of evidence indicating that microtubules and their associated proteins also influence fission and fusion dynamics (Mehta, Chacko, Chug, Jhunjhunwala, & Ananthanarayanan, ; Perdiz, Lorin, Leroy‐Gori, & Pous, ). Actin filaments and their associated proteins also contribute to the fission/fusion balance in cells (DuBoff, Gotz, & Feany, ; Hatch, Ji, Merrill, Strack, & Higgs, ; Ji, Hatch, Merrill, Strack, & Higgs, ; Korobova, Gauvin, & Higgs, ; Korobova, Ramabhadran, & Higgs, ; Manor et al, ), as well as providing an additional system for motor‐based transport through actin–myosin interactions (Kruppa et al, ; Pathak, Sepp, & Hollenbeck, ; Rohn et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…There is a growing body of evidence indicating that microtubules and their associated proteins also influence fission and fusion dynamics (Mehta, Chacko, Chug, Jhunjhunwala, & Ananthanarayanan, 2019;Perdiz, Lorin, Leroy-Gori, & Pous, 2017). Actin filaments and their associated proteins also contribute to the fission/fusion balance in cells (DuBoff, Gotz, & Feany, 2012;Hatch, Ji, Merrill, Strack, & Higgs, 2016;Ji, Hatch, Merrill, Strack, & Higgs, 2015;Korobova, Gauvin, & Higgs, 2014;Korobova, Ramabhadran, & Higgs, 2013;Manor et al, 2015), as well as providing an additional system for motor-based transport through actin-myosin interactions (Kruppa et al, 2018;Pathak, Sepp, & Hollenbeck, 2010;Rohn et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The MyMOMA domain of MYO19 encodes for distinct Miro‐dependent and Miro‐independent mechanisms of interaction with mitochondrial membranes

et al. 2019

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MYO19 interacts with mitochondria through a C‐terminal membrane association domain (MyMOMA). Specific mechanisms for localization of MYO19 to mitochondria are poorly understood. Using promiscuous biotinylation data in combination with existing affinity‐capture databases, we have identified a number of putative MYO19‐interacting proteins. We chose to explore the interaction between MYO19 and the mitochondrial GTPase Miro2 by expressing mchr‐Miro2 in combination with GFP‐tagged fragments of the MyMOMA domain and assaying for recruitment of MYO19‐GFP to mitochondria. Coexpression of MYO19898‐970‐GFP with mchr‐Miro2 enhanced MYO19898‐970‐GFP localization to mitochondria. Mislocalizing Miro2 to filopodial tips or the cytosolic face of the nuclear envelope did not recruit MYO19898‐970‐GFP to either location. To address the kinetics of the Miro2/MYO19 interaction, we used FRAP analysis and permeabilization‐activated reduction in fluorescence analysis. MyMOMA constructs containing a putative membrane‐insertion motif but lacking the Miro2‐interacting region displayed slow exchange kinetics. MYO19898‐970‐GFP, which does not include the membrane‐insertion motif, displayed rapid exchange kinetics, suggesting that MYO19 interacting with Miro2 has higher mobility than MYO19 inserted into the mitochondrial outer membrane. Mutation of well‐conserved, charged residues within MYO19 or within the switch I and II regions of Miro2 abolished the enhancement of MYO19898‐970‐GFP localization in cells ectopically expressing mchr‐Miro2. Additionally, expressing mutant versions of Miro2 thought to represent particular nucleotide states indicated that the enhancement of MYO19898‐970‐GFP localization is dependent on Miro2 nucleotide state. Taken together, these data suggest that membrane‐inserted MYO19 is part of a larger complex, and that Miro2 plays a role in integration of actin‐ and microtubule‐based mitochondrial activities.

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Stress-induced hyperacetylation of microtubule enhances mitochondrial fission and modulates the phosphorylation of Drp1 at 616Ser

Cited by 42 publications

References 46 publications

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

PTBP2-dependent alternative splicing regulates protein transport and mitochondria morphology in post-meiotic germ cells.

The MyMOMA domain of MYO19 encodes for distinct Miro‐dependent and Miro‐independent mechanisms of interaction with mitochondrial membranes

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