The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.

Abstract:

:Mitochondrial dysfunction is an early sign of many neurodegenerative diseases. Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient Parkin recruitment to impaired mitochondria. PD-associated Parkin mutations interfere with the process of mitophagy at distinct steps. Here we show that whole mitochondria are turned over via macroautophagy. Moreover, disease-associated PINK1 mutations also compromise the selective degradation of depolarized mitochondria. This may be due to the decreased physical binding activity of PD-linked PINK1 mutations to Parkin. Thus, PINK1 mutations abrogate autophagy of impaired mitochondria upstream of Parkin. In addition to compromised PINK1 kinase activity, reduced binding of PINK1 to Parkin leads to failure in Parkin mitochondrial translocation, resulting in the accumulation of damaged mitochondria, which may contribute to disease pathogenesis.

journal_name

Autophagy

journal_title

Autophagy

authors

Geisler S,Holmström KM,Treis A,Skujat D,Weber SS,Fiesel FC,Kahle PJ,Springer W

doi

10.4161/auto.6.7.13286

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

871-8

issue

7

eissn

1554-8627

issn

1554-8635

pii

13286

journal_volume

6

pub_type

杂志文章
  • The interplay between PRKCI/PKCλ/ι, SQSTM1/p62, and autophagy orchestrates the oxidative metabolic response that drives liver cancer.

    abstract::Hepatocellular carcinoma (HCC) is the consequence of chronic liver damage caused by the excessive generation of reactive oxygen species (ROS). To mitigate the deleterious effects of ROS, cells activate the transcription factor NFE2L2/NRF2, which is constitutively degraded through its partner KEAP1. The inactivation of...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2020.1797290

    authors: Moscat J,Diaz-Meco MT

    更新日期:2020-10-01 00:00:00

  • Exploiting cell death pathways by an E. coli cytotoxin: autophagy as a double-edged sword for the host.

    abstract::Cytotoxic necrotizing factor 1 is a bacterial protein toxin from Escherichia coli that is able to activate the Rho GTPases and to hinder apoptosis and mitotic catastrophe. Upon exposure to toxin, cells undergo a complex framework of changes, including cytoskeleton remodeling and multinucleation. These cells also show ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.2965

    authors: Fiorentini C,Malorni W

    更新日期:2006-10-01 00:00:00

  • The trehalose-6-phosphate phosphatase Tps2 regulates ATG8 transcription and autophagy in Saccharomyces cerevisiae.

    abstract::Macroautophagy/autophagy is an important catabolic process for maintaining cellular homeostasis by adapting to various stress conditions. Autophagy is mediated by a double-membrane autophagosome, which sequesters a portion of cytoplasmic components for delivery to the vacuole. Several autophagy-related (ATG) genes pla...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1746592

    authors: Kim B,Lee Y,Choi H,Huh WK

    更新日期:2020-04-02 00:00:00

  • A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

    abstract::Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnos...

    journal_title:Autophagy

    pub_type: 杂志文章,多中心研究

    doi:10.4161/auto.28984

    authors: Rosenfeld MR,Ye X,Supko JG,Desideri S,Grossman SA,Brem S,Mikkelson T,Wang D,Chang YC,Hu J,McAfee Q,Fisher J,Troxel AB,Piao S,Heitjan DF,Tan KS,Pontiggia L,O'Dwyer PJ,Davis LE,Amaravadi RK

    更新日期:2014-08-01 00:00:00

  • Autophagy and innate immunity: Insights from invertebrate model organisms.

    abstract::Macroautophagy/autophagy is a fundamental intracellular degradation process with multiple roles in immunity, including direct elimination of intracellular microorganisms via 'xenophagy.' In this review, we summarize studies from the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans that highlig...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2017.1389824

    authors: Kuo CJ,Hansen M,Troemel E

    更新日期:2018-01-01 00:00:00

  • Localized de novo phospholipid synthesis drives autophagosome biogenesis.

    abstract::During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degradation critical to cellular and organismal health. Driven by rapid membrane assembly, an initially small vesicle (phagophore) elongates into a large cup-shaped structure to engulf substrat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1725379

    authors: Schütter M,Graef M

    更新日期:2020-04-01 00:00:00

  • Autophagy by hepatitis B virus and for hepatitis B virus.

    abstract::Autophagy is a catabolic process by which cells remove unwanted proteins and damaged organelles. It is important for maintaining cellular homeostasis and can also be used by cells to remove intracellular microbial pathogens. As such, some viruses such as herpes simplex virus-1 (HSV-1) have evolved mechanisms to suppre...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11669

    authors: Sir D,Ann DK,Ou JH

    更新日期:2010-05-01 00:00:00

  • Potential subversion of autophagosomal pathway by picornaviruses.

    abstract::The RNA replication complexes of small positive-strand RNA viruses such as poliovirus are known to form on the surfaces of membranous vesicles in the cytoplasm of infected mammalian cells. These membranes resemble cellular autophagosomes in their double-membraned morphology, cytoplasmic lumen, lipid-rich composition a...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.5377

    authors: Taylor MP,Kirkegaard K

    更新日期:2008-04-01 00:00:00

  • TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition.

    abstract::The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arre...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1429875

    authors: Lima S,Takabe K,Newton J,Saurabh K,Young MM,Leopoldino AM,Hait NC,Roberts JL,Wang HG,Dent P,Milstien S,Booth L,Spiegel S

    更新日期:2018-01-01 00:00:00

  • Reticulocyte mitophagy: monitoring mitochondrial clearance in a mammalian model.

    abstract::Mitochondria are the primary site of energy production in animal cells. In mitochondria, the flow of electrons through the electron transport chain creates a potential difference across the inner membrane, which is utilized for ATP production. However, due to inherent inefficiencies in electron transport, reactive oxy...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.3.11245

    authors: Zhang J,Ney PA

    更新日期:2010-04-01 00:00:00

  • Discovery of a novel type of autophagy targeting RNA.

    abstract::Regulated degradation of cellular components by lysosomes is essential to maintain biological homeostasis. In mammals, three forms of autophagy, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA), have been identified. Here, we showed a novel type of autophagy, in which RNA is taken up directly into...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.23002

    authors: Fujiwara Y,Furuta A,Kikuchi H,Aizawa S,Hatanaka Y,Konya C,Uchida K,Yoshimura A,Tamai Y,Wada K,Kabuta T

    更新日期:2013-03-01 00:00:00

  • Dismantling the autophagic arsenal when it is time to die: concerted AMBRA1 degradation by caspases and calpains.

    abstract::Under stress conditions cells activate different response pathways which result in cell survival or apoptosis depending on: (1) the nature of the insults, (2) the type, if acute or chronic stress, and (3) how long the stress persists. Generally, autophagy is induced early to sustain cell survival and inhibit cell deat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.20671

    authors: Corazzari M,Fimia GM,Piacentini M

    更新日期:2012-08-01 00:00:00

  • NPC-phagy: selective autophagy of the nuclear pore complexes.

    abstract::Selective autophagy is critical for the regulation of cellular homeostasis in organisms from yeast to humans. This process is a specific degradation pathway for a wide variety of substrates including unwanted cytosolic components, such as protein aggregates, damaged and/or superfluous organelles, and pathogens. Howeve...

    journal_title:Autophagy

    pub_type: 社论

    doi:10.1080/15548627.2020.1798199

    authors: Yin Z,Klionsky DJ

    更新日期:2020-10-01 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

  • A role for chloride transport in lysosomal protein degradation.

    abstract::Loss of the lysosomal chloride transport protein ClC-7 leads to complex phenotypes in mice and man, including osteopetrosis, accumulation of lysosomal storage material, and neurodegeneration. Using novel tissue-specific ClC-7 knockout mice, we have shown that upon loss of ClC-7, lysosomal degradation of endocytosed pr...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.6.1.10590

    authors: Wartosch L,Stauber T

    更新日期:2010-01-01 00:00:00

  • How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensates.

    abstract::Macroautophagy/autophagy mediates the degradation of ubiquitinated aggregated proteins within lysosomes in a process known as aggrephagy. The cargo receptor SQSTM1/p62 condenses aggregated proteins into larger structures and links them to the nascent autophagosomal membrane (phagophore). How the condensation reaction ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1615306

    authors: Turco E,Witt M,Abert C,Bock-Bierbaum T,Su MY,Trapannone R,Sztacho M,Danieli A,Shi X,Zaffagnini G,Gamper A,Schuschnig M,Fracchiolla D,Bernklau D,Romanov J,Hartl M,Hurley JH,Daumke O,Martens S

    更新日期:2019-08-01 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

  • 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

  • Manipulation of autophagy by MIR375 generates antitumor effects in liver cancer.

    abstract::The exploration into the roles of autophagy in tumorigenesis, either as tumor suppressor or tumor promoter, has led to a great increase in the knowledge of cancer development, progression and treatment. However, there is currently no consensus on how to manipulate autophagy to improve antitumor effects. In this study,...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21796

    authors: Chang Y,Lin J,Tsung A

    更新日期:2012-12-01 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

  • ATM loss disrupts the autophagy-lysosomal pathway.

    abstract::ATM (ataxia telangiectasia mutated) protein is found associated with multiple organelles including synaptic vesicles, endosomes and lysosomes, often in cooperation with ATR (ataxia telangiectasia and Rad3 related). Mutation of the ATM gene results in ataxia-telangiectasia (A-T), an autosomal recessive disorder with de...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1805860

    authors: Cheng A,Tse KH,Chow HM,Gan Y,Song X,Ma F,Qian YXY,She W,Herrup K

    更新日期:2020-08-14 00:00:00

  • Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity.

    abstract::BBC3 (BCL2 binding component 3) is a known apoptosis inducer; however, its role in microglial survival remains poorly understood. In addition to the classical transcription factor TRP53, Mir143 is involved in BBC3 expression at the post-transcriptional level. Here, we identify unique roles of Mir143-BBC3 in mediating ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1191723

    authors: Zhang Y,Shen K,Bai Y,Lv X,Huang R,Zhang W,Chao J,Nguyen LK,Hua J,Gan G,Hu G,Yao H

    更新日期:2016-09-01 00:00:00

  • A rapid and high content assay that measures cyto-ID-stained autophagic compartments and estimates autophagy flux with potential clinical applications.

    abstract::The lack of a rapid and quantitative autophagy assay has substantially hindered the development and implementation of autophagy-targeting therapies for a variety of human diseases. To address this critical issue, we developed a novel autophagy assay using the newly developed Cyto-ID fluorescence dye. We first verified...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1017181

    authors: Guo S,Liang Y,Murphy SF,Huang A,Shen H,Kelly DF,Sobrado P,Sheng Z

    更新日期:2015-01-01 00:00:00

  • Identification of the autophagy pathway in a mollusk bivalve, Crassostrea gigas.

    abstract::The Pacific oyster, Crassostrea gigas, is a mollusk bivalve commercially important as a food source. Pacific oysters are subjected to stress and diseases during culture. The autophagy pathway is involved in numerous cellular processes, including responses to starvation, cell death, and microorganism elimination. Autop...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1713643

    authors: Picot S,Faury N,Arzul I,Chollet B,Renault T,Morga B

    更新日期:2020-11-01 00:00:00

  • A role of small heat shock protein B8 (HspB8) in the autophagic removal of misfolded proteins responsible for neurodegenerative diseases.

    abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. As with other age-dependent neurodegenerative disorders, ALS is linked to the presence of misfolded proteins that may perturb several intracellular mechanisms and trigger neu...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13042

    authors: Crippa V,Carra S,Rusmini P,Sau D,Bolzoni E,Bendotti C,De Biasi S,Poletti A

    更新日期:2010-10-01 00:00:00

  • Autophagy alleviates hypoxia-induced blood-brain barrier injury via regulation of CLDN5 (claudin 5).

    abstract::Blood-brain barrier (BBB) disruption is a key event in triggering secondary damage to the central nervous system (CNS) under stroke, and is frequently associated with abnormal macroautophagy/autophagy in brain microvascular endothelial cells (BMECs). However, the underlying mechanism of autophagy in maintaining BBB in...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1851897

    authors: Yang Z,Lin P,Chen B,Zhang X,Xiao W,Wu S,Huang C,Feng D,Zhang W,Zhang J

    更新日期:2020-12-07 00:00:00

  • FTY720 induces necrotic cell death and autophagy in ovarian cancer cells: a protective role of autophagy.

    abstract::FTY720, a sphingosine analog, is a novel immunosuppressant currently undergoing multiple clinical trials for the prevention of organ transplant rejection and treatment of various autoimmune diseases. Recent studies indicate an additional cytotoxic effect of FTY720 and its preclinical efficacy in a variety of cancer mo...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13614

    authors: Zhang N,Qi Y,Wadham C,Wang L,Warren A,Di W,Xia P

    更新日期:2010-11-01 00:00:00

  • The GID ubiquitin ligase complex is a regulator of AMPK activity and organismal lifespan.

    abstract::The AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by sensing the metabolic status of the cell. AMPK is regulated by phosphorylation and dephosphorylation as a result of changing AMP/ATP levels and by removal of inhibitory ubiquitin residues by USP10. In this context, we identified the GID-c...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1695399

    authors: Liu H,Ding J,Köhnlein K,Urban N,Ori A,Villavicencio-Lorini P,Walentek P,Klotz LO,Hollemann T,Pfirrmann T

    更新日期:2020-09-01 00:00:00

  • How to interpret LC3 immunoblotting.

    abstract::Microtubule-associated protein light chain 3 (LC3) is now widely used to monitor autophagy. One approach is to detect LC3 conversion (LC3-I to LC3-II) by immunoblot analysis because the amount of LC3-II is clearly correlated with the number of autophagosomes. However, LC3-II itself is degraded by autophagy, making int...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.4600

    authors: Mizushima N,Yoshimori T

    更新日期:2007-11-01 00:00:00

  • Autophagy and post-ischemic conditioning in retinal ischemia.

    abstract::Retinal ischemia is a major cause of vision loss and a common underlying mechanism associated with diseases, such as diabetic retinopathy and central retinal artery occlusion. We have previously demonstrated the robust neuroprotection in retina induced by post-conditioning (post-C), a brief period of ischemia, 24 h, f...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1767371

    authors: Mathew B,Chennakesavalu M,Sharma M,Torres LA,Stelman CR,Tran S,Patel R,Burg N,Salkovski M,Kadzielawa K,Seiler F,Aldrich LN,Roth S

    更新日期:2020-05-26 00:00:00