ArticlePloS one2014
Autophagic-lysosomal inhibition compromises ubiquitin-proteasome system performance in a p62 dependent manner in cardiomyocytes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Gap junction protein connexin 36 proteostatic mechanisms in photoreceptor cells subjected to excitotoxic stress.Acta biochimica Polonica · 2026Article
- TLR-mediated aggresome-like induced structures comprise antimicrobial peptides and attenuate intracellular bacterial survival.Molecular biology of the cell · 2024Article
- ER-associated degradation in cystinosis pathogenesis and the prospects of precision medicine.The Journal of clinical investigation · 2023Article
- Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.International journal of molecular sciences · 2023Review
- Protein homeostasis in the aged and diseased heart.The journal of cardiovascular aging · 2023Article
- Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models.Food & function · 2021Article
- Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy.Nature communications · 2021Article
- Endoplasmic Reticulum Stress-Mediated p62 Downregulation Inhibits Apoptosis via c-Jun Upregulation.Biomolecules & therapeutics · 2021Article
- CYLD exaggerates pressure overload-induced cardiomyopathy via suppressing autolysosome efflux in cardiomyocytes.Journal of molecular and cellular cardiology · 2020Article
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Increased clusterin levels after myocardial infarction is due to a defect in protein degradation systems activity.Cell death & disease · 2019Article
- Chronic Alcohol Consumption Inhibits Autophagy and Promotes Apoptosis in the Liver.International journal of medical sciences · 2018Article
- The TRPV1 ion channel regulates thymocyte differentiation by modulating autophagy and proteasome activity.Oncotarget · 2017Article
- Autophagy modulation: a potential therapeutic approach in cardiac hypertrophy.American journal of physiology. Heart and circulatory physiology · 2017Review
- Lumbee traditional medicine: Neuroprotective activities of medicinal plants used to treat Parkinson's disease-related symptoms.Journal of ethnopharmacology · 2017Article
- Review
- Systemic inhibition of neddylation by 3-day MLN4924 treatment regime does not impair autophagic flux in mouse hearts and brains.American journal of cardiovascular disease · 2017Article
- Contribution of p62 to Phenotype Transition of Coronary Arterial Myocytes with Defective Autophagy.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Intracellular protein degradation is primarily performed by the ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP). The interplay between these two pathways has been rarely examined in intact animals and the mechanism underlying the interplay remains unclear. Hence, we sought to test in vivo and in vitro the impact of inhibition of the ALP on UPS proteolytic performance in cardiomyocytes and to explore the underlying mechanism. Transgenic mice ubiquitously expressing a surrogate UPS substrate (GFPdgn) were treated with bafilomycin-A1 (BFA) to inhibit the ALP. Myocardial and renal GFPdgn protein levels but not mRNA levels were increased at 24 hours but not 3 hours after the first injection of BFA. Myocardial protein abundance of key proteasome subunits and the activities of proteasomal peptidases were not discernibly altered by the treatment. In cultured neonatal rat ventricular myocytes (NRVMs), the surrogate UPS substrate GFPu and a control red fluorescence protein (RFP) were co-expressed to probe UPS performance. At 12 hours or 24 hours after ALP inhibition by 3-methyladenine (3-MA) or BFA, GFPu/RFP protein ratios and the protein half-life of GFPu were significantly increased, which is accompanied by increases in p62 proteins. Similar findings were obtained when ALP was inhibited genetically via silencing Atg7 or Rab7. ALP inhibition-induced increases in GFPu and p62 are co-localized in NRVMs. siRNA-mediated p62 knockdown prevented ALP inhibition from inducing GFPu accumulation in NRVMs. We conclude that in a p62-dependent fashion, ALP inhibition impairs cardiac UPS proteolytic performance in cardiomyocytes in vitro and in vivo.
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Registered trials
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