Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial.

Abstract:

:A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients.

journal_name

Autophagy

journal_title

Autophagy

authors

Castagnaro S,Pellegrini C,Pellegrini M,Chrisam M,Sabatelli P,Toni S,Grumati P,Ripamonti C,Pratelli L,Maraldi NM,Cocchi D,Righi V,Faldini C,Sandri M,Bonaldo P,Merlini L

doi

10.1080/15548627.2016.1231279

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

2484-2495

issue

12

eissn

1554-8627

issn

1554-8635

journal_volume

12

pub_type

临床试验,杂志文章
  • The "found-art vacuole"-people learn in different ways.

    abstract::Based on my reading, and on my own experience, I have come to realize that people learn in different ways, and this can include the use of different media. This is one reason I have worked with various artists to portray the topic of autophagy through paintings, music and dance. Indeed, comments from members of the au...

    journal_title:Autophagy

    pub_type: 评论,社论

    doi:10.1080/15548627.2019.1630225

    authors: Klionsky DJ

    更新日期:2019-09-01 00:00:00

  • Downregulation of autophagy by herpesvirus Bcl-2 homologs.

    abstract::The critical role of the cellular autophagy pathway in viral infection and pathogenesis has become increasingly apparent. Mounting evidences suggest that viruses have developed different strategies to meticulously modulate intracellular autophagy for their own benefits, thereby either promoting efficient viral replica...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.5210

    authors: Liang C,E X,Jung JU

    更新日期:2008-04-01 00:00:00

  • Autophagy: a new player in hepatic stellate cell activation.

    abstract::Hepatic stellate cell (HSC) activation, the transition from a resident quiescent HSC to a myofibroblastic collagen-producing HSC, is a fundamental feature of liver fibrosis. Autophagy has been implicated in major liver pathologies, such as HCV infection and hepatocarcinoma. However, its role in HSC biology is largely ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.8.1.18105

    authors: Thoen LF,Guimarães EL,Grunsven LA

    更新日期:2012-01-01 00:00:00

  • Denervation-induced oxidative stress and autophagy signaling in muscle.

    abstract::Alterations in contractile activity influence the intracellular homeostasis of muscle, which results in adaptations in the performance and the phenotype of this tissue. Denervation is an effective disuse model that functions to change the intracellular environment of muscle leading to a rapid loss in mass, a decrease ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.2.7391

    authors: O'Leary MF,Hood DA

    更新日期:2009-02-01 00:00:00

  • Autophagy-inducing peptides from mammalian VSV and fish VHSV rhabdoviral G glycoproteins (G) as models for the development of new therapeutic molecules.

    abstract::It has not been elucidated whether or not autophagy is induced by rhabdoviral G glycoproteins (G) in vertebrate organisms for which rhabdovirus infection is lethal. Our work provides the first evidence that both mammalian (vesicular stomatitis virus, VSV) and fish (viral hemorrhagic septicemia virus, VHSV, and spring ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.29557

    authors: García-Valtanen P,Ortega-Villaizán Mdel M,Martínez-López A,Medina-Gali R,Pérez L,Mackenzie S,Figueras A,Coll JM,Estepa A

    更新日期:2014-09-01 00:00:00

  • Macroautophagy: protector in the diabetes drama?

    abstract::Macroautophagy ("autophagy") is regulated by the same insulin-amino acid-mTOR signaling pathway that controls protein synthesis. Although the literature does not so far include any direct studies confirming this, we expect autophagy to increase during insulin resistance. We discuss the possibility that this may be a u...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4449

    authors: Meijer AJ,Codogno P

    更新日期:2007-09-01 00:00:00

  • A role for TOR complex 2 signaling in promoting autophagy.

    abstract::The conserved target of rapamycin (TOR) kinase is a central regulator of cell growth in response to nutrient availability. TOR forms 2 structurally and functionally distinct complexes, TORC1 and TORC2, and negatively regulates autophagy via TORC1. Here we demonstrate TOR also operates independently through the TORC2 s...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.36262

    authors: Vlahakis A,Powers T

    更新日期:2014-01-01 00:00:00

  • The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins.

    abstract::The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end r...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1222991

    authors: Jiang Y,Lee J,Lee JH,Lee JW,Kim JH,Choi WH,Yoo YD,Cha-Molstad H,Kim BY,Kwon YT,Noh SA,Kim KP,Lee MJ

    更新日期:2016-11-01 00:00:00

  • ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding.

    abstract::Protein synthesis and autophagy work as two opposing processes to control cell growth in response to nutrient supply. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) pathway, which acts as a master regulator to control protein synthesis, has recently been shown to inhibit autophagy by phosphorylating ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.7.15491

    authors: Dunlop EA,Hunt DK,Acosta-Jaquez HA,Fingar DC,Tee AR

    更新日期:2011-07-01 00:00:00

  • Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy.

    abstract::The accumulation of ubiquitin-positive protein aggregates has been implicated in the pathogenesis of neurodegenerative diseases, heart disease and diabetes. Emerging evidence indicates that the autophagy lysosomal pathway plays a critical role in the clearance of ubiquitin aggregates, a process that is mediated by the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.5.12189

    authors: Fan W,Tang Z,Chen D,Moughon D,Ding X,Chen S,Zhu M,Zhong Q

    更新日期:2010-07-01 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

  • Role of actin in shaping autophagosomes.

    abstract::One of the main unanswered questions regarding the early steps of macroautophagy/autophagy is the mechanism of membrane-modeling events required for autophagosome formation. Three independent studies have recently revealed an actin cytoskeleton involvement in this process, providing significant details regarding the r...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1236877

    authors: Zientara-Rytter K,Subramani S

    更新日期:2016-12-01 00:00:00

  • Lysosomal calcium regulates autophagy.

    abstract::Recent evidence has indicated that the lysosome is able to act as a signaling organelle that senses nutrient availability and generates an adaptive response that is important for cellular homeostasis. We recently discovered another example of lysosomal signaling where lysosomal calcium release activates the master aut...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2015.1047130

    authors: Medina DL,Ballabio A

    更新日期:2015-01-01 00:00:00

  • Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis.

    abstract::The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: in the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and has become an important therapeutic target for AD and other neurodegenerative diseases. ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.7.15596

    authors: Yang DS,Stavrides P,Mohan PS,Kaushik S,Kumar A,Ohno M,Schmidt SD,Wesson DW,Bandyopadhyay U,Jiang Y,Pawlik M,Peterhoff CM,Yang AJ,Wilson DA,St George-Hyslop P,Westaway D,Mathews PM,Levy E,Cuervo AM,Nixon RA

    更新日期:2011-07-01 00:00:00

  • Unconventional autophagy mediated by the WD40 domain of ATG16L1 is derailed by the T300A Crohn disease risk polymorphism.

    abstract::A coding polymorphism of the critical autophagic effector ATG16L1 (T300A) increases the risk of Crohn disease, but how this mutation influences the function of ATG16L1 has remained unclear. In a recent report, we showed that the A300 allele alters the ability of the C-terminal WD40 domain of ATG16L1 to interact with p...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1216303

    authors: Serramito-Gómez I,Boada-Romero E,Pimentel-Muiños FX

    更新日期:2016-11-01 00:00:00

  • Jurassic PARK2: You eat your mitochondria, and you are what your mitochondria eat.

    abstract::Park2/Parkin is a central mediator of selective mitochondrial autophagy for mitochondrial quality control. We showed in mouse hearts that PINK1/Mfn2/Park2 mediated generalized mitophagy is essential to the normal perinatal transition from fetal mitochondria that prefer carbohydrates as metabolic substrates to adult fa...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1143210

    authors: Dorn GW 2nd

    更新日期:2016-01-01 00:00:00

  • The COP9 signalosome coerces autophagy and the ubiquitin-proteasome system to police the heart.

    abstract::We demonstrated for the first time that the COP9 signalosome (COPS) controls the degradation of a surrogate and a bona fide misfolded protein in the cytosol of cardiomyocytes likely via supporting ubiquitination by CUL/cullin-RING ligases, and that Cops8 hypomorphism exacerbates cardiac proteinopathy in mice, in which...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1136773

    authors: Liu J,Su H,Wang X

    更新日期:2016-01-01 00:00:00

  • Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance.

    abstract::Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (CSCs). We have recently shown that autophagy is essential for the tumorigenicity of these CSCs. Salinomycin (Sal), a K (+) /H (+) ionophore, has recently been shown to be at l...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.23997

    authors: Yue W,Hamaï A,Tonelli G,Bauvy C,Nicolas V,Tharinger H,Codogno P,Mehrpour M

    更新日期:2013-05-01 00:00:00

  • MLKL contributes to Western diet-induced liver injury through inhibiting autophagy.

    abstract::Macroautophagy/autophagy is critical in maintaining cellular functions and homeostasis. Dynamic regulation of autophagy is associated with development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); however, the mechanisms involved in the regulation of autophagy in NAFLD/NASH are n...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1760624

    authors: Wu X,Nagy LE

    更新日期:2020-07-01 00:00:00

  • Mitochondrial quality control mediated by PINK1 and PRKN: links to iron metabolism and tumor immunity.

    abstract::Mitochondrial quality control is an essential process required to maintain cellular homeostasis and functions. Mutations of PINK1 and PRKN/PARK2 contribute to the risk of Parkinson disease. Our recent findings indicate that depletion of Pink1 and Prkn promotes pancreatic tumorigenesis in KRAS-driven engineered mouse m...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2018.1526611

    authors: Kang R,Xie Y,Zeh HJ,Klionsky DJ,Tang D

    更新日期:2019-01-01 00:00:00

  • Cell-autonomous, paracrine and neuroendocrine feedback regulation of autophagy by DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein): the obesity factor.

    abstract::DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in ...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2019.1662585

    authors: Bravo-San Pedro JM,Sica V,Martins I,Anagnostopoulos G,Maiuri C,Kroemer G

    更新日期:2019-11-01 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

  • Role of autophagy in the host defense against Toxoplasma gondii in astrocytes.

    abstract::Autophagy has recently been implicated in the host defense against the intracellular protozoan pathogen, Toxoplasma gondii, a major opportunistic pathogen of the central nervous system in immunosuppressed individuals. In both IFN gamma-activated macrophages and astrocytes, the p47 GTPases traffic to the T. gondii para...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.2.7637

    authors: Halonen SK

    更新日期:2009-02-01 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

  • TBC1D20 mediates autophagy as a key regulator of autophagosome maturation.

    abstract::In humans, loss of TBC1D20 (TBC1 domain family, member 20) protein function causes Warburg Micro syndrome 4 (WARBM4), an autosomal recessive disorder characterized by congenital eye, brain, and genital abnormalities. TBC1D20-deficient mice exhibit ocular abnormalities and male infertility. TBC1D20 is a ubiquitously ex...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1199300

    authors: Sidjanin DJ,Park AK,Ronchetti A,Martins J,Jackson WT

    更新日期:2016-10-02 00:00:00

  • NUPR1 works against the metabolic stress-induced autophagy-associated cell death in pancreatic cancer cells.

    abstract::The incidence of pancreatic adenocarcinoma is increasing with more than 43,000 predicted new cases in the US and 65,000 in Europe this year. Pancreatic cancer patients have a short life expectancy with less than 3-4% 5-y survival, which results in an equivalent incidence and mortality rate. One of the major challenges...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.22258

    authors: Hamidi T,Cano CE,Grasso D,Garcia MN,Sandi MJ,Calvo EL,Dagorn JC,Lomberk G,Goruppi S,Urrutia R,Carracedo A,Velasco G,Iovanna JL

    更新日期:2013-01-01 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

  • Vitamin D improves sunburns by increasing autophagy in M2 macrophages.

    abstract::Cutaneous inflammation from UV radiation exposure causes epidermal damage, cellular infiltration, and secretion of pro-inflammatory mediators that exacerbate tissue destruction. Recovery is mediated chiefly by anti-inflammatory M2 macrophages that suppress inflammation and augment epidermal regeneration. Vitamin D ena...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1569298

    authors: Das LM,Binko AM,Traylor ZP,Peng H,Lu KQ

    更新日期:2019-05-01 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

  • Rapamycin and Alzheimer disease: a double-edged sword?

    abstract::Numerous studies have reported that inhibition of MTOR (mechanistic target of rapamycin kinase) clearly reduces Alzheimer disease neuropathological hallmarks in mouse models. This has resulted in calls for the use of the MTOR inhibitor rapamycin for the treatment of dementia in humans. Unfortunately, intervention with...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2019.1615823

    authors: Carosi JM,Sargeant TJ

    更新日期:2019-08-01 00:00:00