Autophagy as a rescue mechanism in efavirenz-induced mitochondrial dysfunction: a lesson from hepatic cells.

Abstract:

:Efavirenz (EFV) is the most widely used non-nucleoside reverse transcriptase inhibitor applied in highly active antiretroviral therapy (HAART), the combined pharmacological treatment of the human immunodeficiency virus infection. Its use has been associated with the development of several adverse events including hepatotoxicity. The molecular pathogenesis of this effect is poorly understood but recent reports have highlighted features of mitochondrial dysfunction in hepatic cells exposed to clinically relevant concentrations of EFV. In this study, we investigated the activation of autophagy and, in particular, mitophagy, in human hepatic cells exposed to EFV. We detected the presence of altered mitochondria with abnormal morphology and relative increase in mitochondrial mass. Several autophagic markers reveal specific induction of autophagy. Of special note, while moderate levels of EFV activate autophagy, higher concentrations exceeding the threshold of mitochondrial dysfunction, lead to a blockage in the autophagic flux, thus promoting "autophagic stress". Pharmacological inhibition of autophagy exacerbates the deleterious effect of EFV on cell survival/proliferation thereby promoting apoptosis, a finding which points to the fact that autophagy is triggered as a rescue mechanism enabling cell survival. The effect described in this study could be involved in the EFV-associated hepatotoxicity. It may constitute a new mechanism implicated in the genesis of pharmacological liver damage and in the recovery of hepatic homeostasis upon a drug-induced cellular insult.

journal_name

Autophagy

journal_title

Autophagy

authors

Apostolova N,Gomez-Sucerquia LJ,Gortat A,Blas-Garcia A,Esplugues JV

doi

10.4161/auto.7.11.17653

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

1402-4

issue

11

eissn

1554-8627

issn

1554-8635

pii

17653

journal_volume

7

pub_type

杂志文章
  • Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment.

    abstract::SNCA/α-synuclein aggregation plays a crucial role in synucleinopathies such as Parkinson disease and dementia with Lewy bodies. Aggregating and nonaggregating SNCA species are degraded by the autophagy-lysosomal pathway (ALP). Previously, we have shown that the ALP is not only responsible for SNCA degradation but is a...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.36436

    authors: Poehler AM,Xiang W,Spitzer P,May VE,Meixner H,Rockenstein E,Chutna O,Outeiro TF,Winkler J,Masliah E,Klucken J

    更新日期:2014-01-01 00:00:00

  • Autophagic degradation of SQSTM1 inhibits ovarian cancer motility by decreasing DICER1 and AGO2 to induce MIRLET7A-3P.

    abstract::The relationship between macroautophagy/autophagy and miRNA in regulating cancer cell motility is not clearly delineated. Here, we found that induction of BECN1-dependent or -independent autophagy decreased ubiquitin-binding proteins SQSTM1/p62 and CALCOCO2/NDP52. Downregulation of SQSTM1 (but not CALCOCO2) led to a d...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1501135

    authors: Liao CC,Ho MY,Liang SM,Liang CM

    更新日期:2018-01-01 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

  • PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.

    abstract::Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway h...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1017190

    authors: Ito S,Araya J,Kurita Y,Kobayashi K,Takasaka N,Yoshida M,Hara H,Minagawa S,Wakui H,Fujii S,Kojima J,Shimizu K,Numata T,Kawaishi M,Odaka M,Morikawa T,Harada T,Nishimura SL,Kaneko Y,Nakayama K,Kuwano K

    更新日期:2015-01-01 00:00:00

  • Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon.

    abstract::ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise action of E1, E2, and E3 enzymes. Conjugated ISG15 can be removed (deISGylated) from target proteins by USP18 (ubiquiti...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1023982

    authors: Xu D,Zhang T,Xiao J,Zhu K,Wei R,Wu Z,Meng H,Li Y,Yuan J

    更新日期:2015-04-03 00:00:00

  • Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

    abstract::Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated eth...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.18997

    authors: Guo R,Hu N,Kandadi MR,Ren J

    更新日期:2012-04-01 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

  • Autophagy and access: understanding the role of androgen receptor subcellular localization in SBMA.

    abstract::Ridding neurons of toxic misfolded proteins is a critical feature of many neurodegenerative diseases. We have recently reported that lack of access of nuclear polyglutamine-expanded androgen receptor (AR) to the autophagic degradation pathway is a critical point in pathogenesis. When mutant AR is contained within the ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.8.9726

    authors: Montie HL,Merry DE

    更新日期:2009-11-01 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

  • Harpooning the Cvt complex to the phagophore assembly site.

    abstract::Autophagy is a catabolic process employed by eukaryotes to degrade and recycle intracellular components. When this pathway is induced by starvation conditions, part of the cytoplasm and organelles are sequestered into double-membrane vesicles called autophagosomes, and delivered into the lysosome/vacuole for degradati...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6657

    authors: Monastyrska I,Reggiori F,Klionsky DJ

    更新日期:2008-10-01 00:00:00

  • How autophagy regulates the host cell signaling associated with the postpartum bacteria cocoon experienced as a danger signal.

    abstract::Shigella, the causative agent of human bacillary dysentery, invades the host cell, rapidly breaking the phagosome and multiplying in the cytosol. Here, we summarize our recent work showing the targeting of the leftover membrane remnants to autophagy together with trapped membrane-associated signaling molecules recruit...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.8.10218

    authors: Dupont N,Lafont F

    更新日期:2009-11-01 00:00:00

  • Autophagy and proteotoxicity in cardiomyocytes.

    abstract::Increasing evidence suggests that misfolded proteins and intracellular aggregates contribute to cardiac disease and heart failure. We wished to determine if autophagic induction by Atg7 is sufficient to reduce misfolded protein and aggregate content in protein misfolding-stressed cardiomyocytes. We used loss- and gain...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.10.16882

    authors: Pattison JS,Robbins J

    更新日期:2011-10-01 00:00:00

  • Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages.

    abstract::Phagocytosis of naturally dying cells usually blocks inflammatory reactions in host cells. We have recently observed that clearance of cells dying through autophagy leads to a pro-inflammatory response in human macrophages. Investigating this response further, we found that during engulfment of MCF-7 or 293T cells und...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.3.14583

    authors: Petrovski G,Ayna G,Majai G,Hodrea J,Benko S,Mádi A,Fésüs L

    更新日期:2011-03-01 00:00:00

  • The axis of MAPK1/3-XBP1u-FOXO1 controls autophagic dynamics in cancer cells.

    abstract::Earlier studies have shown that macroautophagy is not a constitutively activated process, however, the mechanism of activation is not fully understood. Here, we report that autophagy is a dynamic process in cancer cells in response to glucose starvation. In addition, we determined that FOXO1 turnover is involved in th...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.23918

    authors: Zhao Y,Li X,Ma K,Yang J,Zhou J,Fu W,Wei F,Wang L,Zhu WG

    更新日期:2013-05-01 00:00:00

  • Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling.

    abstract::Quercetin, a dietary antioxidant present in fruits and vegetables, is a promising cancer chemopreventive agent that inhibits tumor promotion by inducing cell cycle arrest and promoting apoptotic cell death. In this study, we examined the biological activities of quercetin against gastric cancer. Our studies demonstrat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.9.15863

    authors: Wang K,Liu R,Li J,Mao J,Lei Y,Wu J,Zeng J,Zhang T,Wu H,Chen L,Huang C,Wei Y

    更新日期:2011-09-01 00:00:00

  • Mitochondrial elongation during autophagy: a stereotypical response to survive in difficult times.

    abstract::Mitochondrial morphological and structural changes play a role in several cellular processes, including apoptosis. We recently reported that mitochondrial elongation is also critical to sustain cell viability during macroautophagy. During macroautophagy unopposed mitochondrial fusion leads to organelle elongation both...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.10.16771

    authors: Gomes LC,Scorrano L

    更新日期:2011-10-01 00:00:00

  • BECN1 is a new driver of ferroptosis.

    abstract::Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferropto...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2018.1513758

    authors: Kang R,Zhu S,Zeh HJ,Klionsky DJ,Tang D

    更新日期:2018-01-01 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

  • HIF1A Alleviates compression-induced apoptosis of nucleus pulposus derived stem cells via upregulating autophagy.

    abstract::Intervertebral disc degeneration (IDD) is the primary pathological mechanism that underlies low back pain. Overloading-induced cell death, especially endogenous stem cell death, is the leading factor that undermines intrinsic repair and aggravates IDD. Previous research has separately studied the effect of oxygen conc...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872227

    authors: He R,Wang Z,Cui M,Liu S,Wu W,Chen M,Wu Y,Qu Y,Lin H,Chen S,Wang B,Shao Z

    更新日期:2021-01-18 00:00:00

  • Role of Arabidopsis RabG3b and autophagy in tracheary element differentiation.

    abstract::The vascular system of plants consists of two conducting tissues, xylem and phloem, which differentiate from procambium cells. Xylem serves as a transporting system for water and signaling molecules and is formed by sequential developmental processes, including cell division/expansion, secondary cell wall deposition, ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13429

    authors: Kwon SI,Cho HJ,Park OK

    更新日期:2010-11-01 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

  • Autophagy delays apoptosis in renal tubular epithelial cells in cisplatin cytotoxicity.

    abstract::One of the major side effects of cisplatin chemotherapy is toxic acute kidney injury due to preferential accumulation of cisplatin in renal proximal tubule epithelial cells and the subsequent injury to these cells. Apoptosis is known as a major mechanism of cisplatin-induced cell death in renal tubular cells. We have ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.6309

    authors: Kaushal GP,Kaushal V,Herzog C,Yang C

    更新日期:2008-07-01 00:00:00

  • Multistep regulation of TFEB by MTORC1.

    abstract::The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is pho...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1271514

    authors: Vega-Rubin-de-Celis S,Peña-Llopis S,Konda M,Brugarolas J

    更新日期:2017-03-04 00:00:00

  • Upregulation of ATG7 attenuates motor neuron dysfunction associated with depletion of TARDBP/TDP-43.

    abstract::A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patie...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1635379

    authors: Donde A,Sun M,Jeong YH,Wen X,Ling J,Lin S,Braunstein K,Nie S,Wang S,Chen L,Wong PC

    更新日期:2020-04-01 00:00:00

  • HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting.

    abstract::Infection and inflammation are able to induce diet-independent Na+-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na+-boosted host defense against the protozoan ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1596483

    authors: Neubert P,Weichselbaum A,Reitinger C,Schatz V,Schröder A,Ferdinand JR,Simon M,Bär AL,Brochhausen C,Gerlach RG,Tomiuk S,Hammer K,Wagner S,van Zandbergen G,Binger KJ,Müller DN,Kitada K,Clatworthy MR,Kurts C,Titze J,

    更新日期:2019-11-01 00:00:00

  • KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression.

    abstract::We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occu...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1235122

    authors: Santarelli R,Granato M,Pentassuglia G,Lacconi V,Gilardini Montani MS,Gonnella R,Tafani M,Torrisi MR,Faggioni A,Cirone M

    更新日期:2016-12-01 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

  • Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy.

    abstract::Oxidative stress-induced granulosa cell (GCs) death represents a common reason for follicular atresia. Follicle-stimulating hormone (FSH) has been shown to prevent GCs from oxidative injury, although the underlying mechanism remains to be elucidated. Here we first report that the suppression of autophagic cell death v...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1327941

    authors: Shen M,Jiang Y,Guan Z,Cao Y,Li L,Liu H,Sun SC

    更新日期:2017-08-03 00:00:00

  • Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection.

    abstract::Autophagy has been recently proposed to be a component of the innate cellular immune response against several types of intracellular microorganisms. However, other intracellular bacteria including Listeria monocytogenes have been thought to evade the autophagic cellular surveillance. Here, we show that cellular infect...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.3618

    authors: Py BF,Lipinski MM,Yuan J

    更新日期:2007-03-01 00:00:00

  • LAMP-2: a control step for phagosome and autophagosome maturation.

    abstract::The two structurally related, major lysosomal membrane proteins LAMP-1 and LAMP-2 were for a long time regarded as crucial for the protection of the lysosomal membrane from the hostile lumenal environment. However, recent studies on the effects of single and combined LAMP-deficiency in mice reveal alternative function...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5724

    authors: Saftig P,Beertsen W,Eskelinen EL

    更新日期:2008-05-01 00:00:00