Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the apoptosis of hypoxia/reoxygenation-induced cardiomyocytes.

Abstract:

:Post-translational modifications of autophagy-related (ATG) genes are necessary to modulate their functions. However, ATG protein methylation and its physiological role have not yet been elucidated. The methylation of non-histone proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. Here we present evidence that the precise activity of ATG16L1 protein in hypoxia/reoxygenation (H/R)-treated cardiomyocytes is regulated by a balanced methylation and phosphorylation switch. We first show that H/R promotes autophagy and decreases SETD7 expression, whereas autophagy inhibition by 3-MA increases SETD7 level in cardiomyocytes, implying a tight correlation between autophagy and SETD7. Then we demonstrate that SETD7 methylates ATG16L1 at lysine 151 while KDM1A/LSD1 (lysine demethylase 1A) removes this methyl mark. Furthermore, we validate that this methylation at lysine 151 impairs the binding of ATG16L1 to the ATG12-ATG5 conjugate, leading to inhibition of autophagy and increased apoptosis in H/R-treated cardiomyocytes. However, the cardiomyocytes with shRNA-knocked down SETD7 or inhibition of SETD7 activity by a small molecule chemical, display increased autophagy and decreased apoptosis following H/R treatment. Additionally, methylation at lysine 151 inhibits phosphorylation of ATG16L1 at S139 by CSNK2 which was previously shown to be critical for autophagy maintenance, and vice versa. Together, our findings define a novel modification of ATG16L1 and highlight the importance of an ATG16L1 phosphorylation-methylation switch in determining the fate of H/R-treated cardiomyocytes.

journal_name

Autophagy

journal_title

Autophagy

authors

Song H,Feng X,Zhang M,Jin X,Xu X,Wang L,Ding X,Luo Y,Lin F,Wu Q,Liang G,Yu T,Liu Q,Zhang Z

doi

10.1080/15548627.2017.1389357

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

825-844

issue

5

eissn

1554-8627

issn

1554-8635

journal_volume

14

pub_type

杂志文章
  • MTOR inhibition attenuates DNA damage and apoptosis through autophagy-mediated suppression of CREB1.

    abstract::Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. However, rapamycin has also been found to compromise the efficacy of chemotherapeutics to cells with hyperactive MTOR. Her...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26447

    authors: Wang Y,Hu Z,Liu Z,Chen R,Peng H,Guo J,Chen X,Zhang H

    更新日期:2013-12-01 00:00:00

  • AP-4: autophagy-four mislocalized proteins in axons.

    abstract::Neurons are highly polarized cells composed of two distinct domains, the axon and the somatodendritic domain. Although AMPA-type glutamate receptors, which mediate fast excitatory neurotransmission in the vertebrate CNS, are preferentially expressed in the somatodendritic domain, the molecular mechanisms underlying su...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6493

    authors: Matsuda S,Yuzaki M

    更新日期:2008-08-01 00:00:00

  • Processing of autophagic protein LC3 by the 20S proteasome.

    abstract::Ubiquitin-proteasome system and autophagy are the two major mechanisms for protein degradation in eukaryotic cells. LC3, a ubiquitin-like protein, plays an essential role in autophagy through its ability to be conjugated to phosphatidylethanolamine. In this study, we discovered a novel LC3-processing activity, and bio...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.1.10928

    authors: Gao Z,Gammoh N,Wong PM,Erdjument-Bromage H,Tempst P,Jiang X

    更新日期:2010-01-01 00:00:00

  • The NEDD4-USP13 axis facilitates autophagy via deubiquitinating PIK3C3.

    abstract::Macroautophagy/autophagy, an evolutionarily conserved eukaryotic bioprocess, plays an important role in the bulk degradation of intracellular macromolecules, organelles, and invading pathogens. PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3) functions as a key protein in autophagy initiation and ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1743071

    authors: Xie W,Jin S,Cui J

    更新日期:2020-06-01 00:00:00

  • Decreased neuronal autophagy in HIV dementia: a mechanism of indirect neurotoxicity.

    abstract::Many recent studies indicate that dysregulation of autophagy is a common feature of many neurodegenerative diseases. The HIV-1-associated neurological disorder is an acquired cognitive and motor disease that includes a severe neurodegenerative dementia. We find that the neurodegeneration seen in the brain in HIV-1 inf...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6805

    authors: Alirezaei M,Kiosses WB,Fox HS

    更新日期:2008-10-01 00:00:00

  • Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model.

    abstract::Innate immune defense against intracellular pathogens, like Salmonella, relies heavily on the autophagy machinery of the host. This response is studied intensively in epithelial cells, the target of Salmonella during gastrointestinal infections. However, little is known of the role that autophagy plays in macrophages,...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1569297

    authors: Masud S,Prajsnar TK,Torraca V,Lamers GEM,Benning M,Van Der Vaart M,Meijer AH

    更新日期:2019-05-01 00:00:00

  • Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells.

    abstract::Macroautophagy/autophagy occurs at basal levels in all eukaryotic cells and plays an important role in maintaining bio-energetic homeostasis through the control of molecule degradation and organelle turnover. It can be induced by environmental conditions such as starvation, and is deregulated in many diseases includin...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2019.1630223

    authors: Ceccariglia S,Cargnoni A,Silini AR,Parolini O

    更新日期:2020-01-01 00:00:00

  • Eating on the fly: function and regulation of autophagy during cell growth, survival and death in Drosophila.

    abstract::Significant progress has been made over recent years in defining the normal progression and regulation of autophagy, particularly in cultured mammalian cells and yeast model systems. However, apart from a few notable exceptions, our understanding of the physiological roles of autophagy has lagged behind these advances...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.5782

    authors: Neufeld TP,Baehrecke EH

    更新日期:2008-07-01 00:00:00

  • STAT3 transcriptional factor activated by reactive oxygen species induces IL6 in starvation-induced autophagy of cancer cells.

    abstract::Autophagy is one of the survival processes of cancer cells, especially in stressful conditions such as starvation, hypoxia and chemotherapeutic agents. However, its roles in tumor survival have not yet been fully elucidated. Here, we found for the first time that JAK2/STAT3 was activated in HeLa cells when they were s...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13547

    authors: Yoon S,Woo SU,Kang JH,Kim K,Kwon MH,Park S,Shin HJ,Gwak HS,Chwae YJ

    更新日期:2010-11-01 00:00:00

  • Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell death.

    abstract::Although Beclin 1 and mTOR are considered to be the main molecules to modulate the autophagic process, searching for other autophagy-regulating molecules is still an ongoing challenge to scientists. Here we demonstrated that FoxO1, a forkhead O family protein, is a mediator of autophagy. Upon oxidative stress or serum...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13289

    authors: Zhao Y,Wang L,Yang J,Zhang P,Ma K,Zhou J,Liao W,Zhu WG

    更新日期:2010-10-01 00:00:00

  • Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease.

    abstract::Mitochondrial dysfunction is associated with the occurrence of a variety of neurodegenerative diseases, especially Alzheimer disease (AD). As a mitochondrial quality control process, mitophagy is greatly inhibited in AD; increasing evidence shows that the induction of mitophagy is an effective therapeutic intervention...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1860542

    authors: Cen X,Xu X,Xia H

    更新日期:2020-12-20 00:00:00

  • microRNA 30A promotes autophagy in response to cancer therapy.

    abstract::microRNAs (miRNAs) are a class of small regulatory RNAs that regulate gene expression at the post-transcriptional level. miRNAs play important roles in the regulation of development, growth, and metastasis of cancer, and in determining the response of tumor cells to anticancer therapy. In recent years, they have also ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.20053

    authors: Yu Y,Cao L,Yang L,Kang R,Lotze M,Tang D

    更新日期:2012-05-01 00:00:00

  • Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy.

    abstract::The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training Network was approved under the European Union's Horizon 2020 Research and Innovation Program a...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1515532

    authors: Kraft C,Boya P,Codogno P,Elazar Z,Eskelinen EL,Farrés J,Kirkin V,Jungbluth H,Martinez A,Pless O,Primard C,Proikas-Cezanne T,Simonsen A,Reggiori F

    更新日期:2019-02-01 00:00:00

  • ER-phagy: selective autophagy of the endoplasmic reticulum.

    abstract::Throughout their life, cells must maintain homeostasis while facing constantly fluctuating demands on their different organelles. A major mechanism for the homeostatic control of organelle function is the unfolded protein response (UPR), a signaling pathway that triggers a comprehensive remodeling of the endoplasmic r...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.3930

    authors: Bernales S,Schuck S,Walter P

    更新日期:2007-05-01 00:00:00

  • Implications of autophagy in anthrax pathogenicity.

    abstract::The etiological agent for anthrax is Bacillus anthracis, which produces lethal toxin (LT) that exerts a myriad of effects on many immune cells. In our previous study, it was demonstrated that LT and protective antigen (PA) induce autophagy in mammalian cells. Preliminary results suggest that autophagy may function as ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.5.8567

    authors: Tan YK,Vu HA,Kusuma CM,Wu A

    更新日期:2009-07-01 00:00:00

  • The induction of autophagy by mechanical stress.

    abstract::The ability to respond and adapt to changes in the physical environment is a universal and essential cellular property. Here we demonstrated that cells respond to mechanical compressive stress by rapidly inducing autophagosome formation. We measured this response in both Dictyostelium and mammalian cells, indicating t...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.12.17924

    authors: King JS,Veltman DM,Insall RH

    更新日期:2011-12-01 00:00:00

  • Perturbation of autophagic pathway by hepatitis C virus.

    abstract::Autophagy removes long-lived proteins and damaged organelles and is important for maintaining cellular homeostasis. It can also serve in innate immunity to remove intracellular pathogens. As such, viruses have evolved different mechanisms to subvert this innate immune response. We have recently demonstrated that hepat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6566

    authors: Sir D,Liang C,Chen WL,Jung JU,Ou JH

    更新日期:2008-08-01 00:00:00

  • Unsaturation, curvature and charge: effects of membrane parameters on PIK3C3/VPS34-containing complexes.

    abstract::Phosphatidylinositol-3-phosphate (PtdIns3P) is essential for generating autophagosomes and regulating endocytic trafficking. Recently, we have shown that the activities of human PIK3C3/VPS34-containing complexes I and II, which synthesize PtdIns3P, are greatly affected by three membrane physicochemical parameters: lip...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872190

    authors: Ohashi Y,Tremel S,Williams RL

    更新日期:2021-01-15 00:00:00

  • Inhibition of autophagy enhances the anticancer activity of silver nanoparticles.

    abstract::Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can indu...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.36293

    authors: Lin J,Huang Z,Wu H,Zhou W,Jin P,Wei P,Zhang Y,Zheng F,Zhang J,Xu J,Hu Y,Wang Y,Li Y,Gu N,Wen L

    更新日期:2014-01-01 00:00:00

  • Granulosa cell subtypes respond by autophagy or cell death to oxLDL-dependent activation of the oxidized lipoprotein receptor 1 and toll-like 4 receptor.

    abstract::Autophagic cell death has been observed in granulosa cell cultures via the oxLDL-dependent activation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1). This activation might differ for cytokeratin-positive (CK(+)) and CK(-) granulosa cells. In particular, LOX-1 and toll-like receptor 4 (TLR4), one of...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.7.9507

    authors: Serke H,Vilser C,Nowicki M,Hmeidan FA,Blumenauer V,Hummitzsch K,Lösche A,Spanel-Borowski K

    更新日期:2009-10-01 00:00:00

  • Purification of autophagosomes from rat hepatocytes.

    abstract::To facilitate the purification of rat liver autophagosomes, isolated rat hepatocytes are first incubated for 2 h at 37°C with vinblastine, which induces autophagosome accumulation by blocking the fusion of these organelles with endosomes and lysosomes. The hepatocytes are then electrodisrupted and homogenized, and the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11272

    authors: Seglen PO,Brinchmann MF

    更新日期:2010-05-01 00:00:00

  • Suppressing the dark side of autophagy.

    abstract::A wide variety of genetic, pharmacological and nutrient manipulations that extend lifespan in model organisms do so in a manner dependent upon increased autophagic flux. However, our recent findings suggest that when mitochondrial membrane integrity is compromised, macroautophagy/autophagy can be detrimental. In C. el...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1644077

    authors: Zhou B,Soukas AA

    更新日期:2019-10-01 00:00:00

  • The role of Tecpr1 in selective autophagy as a cargo receptor.

    abstract::Bacterial intrusion of host cells can be recognized by the innate immune system, including autophagy, via multiple cellular pathways. We have identified Tecpr1 as an Atg5-binding partner, and found that Tecpr1 interacts with the Atg12-Atg5-Atg16L1 complex via binding to Atg5. In Shigella infected cells, Tecpr1 colocal...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.11.17151

    authors: Ogawa M,Sasakawa C

    更新日期:2011-11-01 00:00:00

  • Autophagy defects in Lafora disease: cause or consequence?

    abstract::Lafora disease (LD) is an inherited and fatal form of neurodegenerative disorder characterized by the presence of an abnormal form of glycogen inclusions, called Lafora bodies, in neurons and other tissues. While Lafora bodies have been thought to underlie the neuropathology in LD, the specific process by which these ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.8.2.19010

    authors: Puri R,Ganesh S

    更新日期:2012-02-01 00:00:00

  • Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF.

    abstract::Recent evidence suggests that autophagy may favor fibrosis through enhanced differentiation of fibroblasts in myofibroblasts. Here, we sought to characterize the mediators and signaling pathways implicated in autophagy-induced myofibroblast differentiation. Fibroblasts, serum starved for up to 4 d, showed increased LC...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/15548627.2014.981786

    authors: Bernard M,Dieudé M,Yang B,Hamelin K,Underwood K,Hébert MJ

    更新日期:2014-01-01 00:00:00

  • Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking.

    abstract::Glioblastoma is one of the most aggressive human cancers with poor prognosis, and therefore a critical need exists for novel therapeutic strategies for management of glioblastoma patients. Itraconazole, a traditional antifungal drug, has been identified as a novel potential anticancer agent due to its inhibitory effec...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.28912

    authors: Liu R,Li J,Zhang T,Zou L,Chen Y,Wang K,Lei Y,Yuan K,Li Y,Lan J,Cheng L,Xie N,Xiang R,Nice EC,Huang C,Wei Y

    更新日期:2014-07-01 00:00:00

  • Increased expression of ATG genes during nonfeeding periods in the tick Haemaphysalis longicornis.

    abstract::Ticks are long-lived hematophagous arthropods and have tolerance to starvation. They can survive without food during the host-seeking period for several months to years. To understand how ticks obtain energy over a long period of non-feeding (starvation), we focused on autophagy, a crucial proteolysis system via the l...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11668

    authors: Umemiya-Shirafuji R,Matsuo T,Liao M,Boldbaatar D,Battur B,Suzuki H,Fujisaki K

    更新日期:2010-05-01 00:00:00

  • Progesterone receptor membrane component 1/Sigma-2 receptor associates with MAP1LC3B and promotes autophagy.

    abstract::Autophagy resembles a recycling process in which proteins, organelles, or regions of the cytoplasm are enveloped and degraded. We have found that two of the central autophagy proteins, MAP1LC3 (microtubule-associated protein 1 light chain 3, also described as LC3) and UVRAG (UV radiation resistance associated/UV radia...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.25889

    authors: Mir SU,Schwarze SR,Jin L,Zhang J,Friend W,Miriyala S,St Clair D,Craven RJ

    更新日期:2013-10-01 00:00:00

  • PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy.

    abstract::Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome bi...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1226735

    authors: Dias MV,Teixeira BL,Rodrigues BR,Sinigaglia-Coimbra R,Porto-Carreiro I,Roffé M,Hajj GN,Martins VR

    更新日期:2016-11-01 00:00:00

  • Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans.

    abstract::Autophagy is a conserved membrane trafficking pathway that mediates the delivery of cytoplasmic substrates to the lysosome for degradation. Impaired autophagic function is implicated in the pathology of various neurodegenerative diseases. We have generated transgenic C. elegans that express human beta-amyloid peptide ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4776

    authors: Florez-McClure ML,Hohsfield LA,Fonte G,Bealor MT,Link CD

    更新日期:2007-11-01 00:00:00