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pubmed, article, google, scholar, cas, central, mitochondrial, singh, cell, autophagy, antibiotics, mitochondria, research, cells, biol, function, supplementary, material, lysosomal, death, biophys, biogenesis, prajapati, springer, mitophagy, biochim, acta, university, content, human, bhatelia, mol, india, author, jpeg, privacy, cookies, sripada, rochika, rajesh, side, activation, lysosome, stress, apoptosis, degradation, chem, science, usa, information,

Topics {✒️}

grant number—sb/ft/ls-285/2012 month download article/chapter side effects due khyati bhatelia received wang-xia wang & joe side effects targeting inter-organelle crosstalk p62/sqstm1 binds directly cldm-induced cell death aminoglycoside-induced hearing loss wang-xia wang full article pdf rajesh singh kritarth singh khyati bhatelia side effect senior research fellowship monitor ros production selective autophagy mediated reactive oxygen species article molecular antibiotics alter mitochondria front-line treatment privacy choices/manage cookies mammalian autophagy research cellular biochemistry aims underlying molecular mechanisms check access instant access lysosome interactions leading article prajapati antenatal antibiotic exposure balancing mitochondrial biogenesis falcon-perez jm central role lysosomal membrane degradation related subjects autophagosome-lysosome fusion permeabilizes cytoplasmic membrane induces cell death lysosomal lipid degradation monitoring mitochondrial turnover vacuolar proton pumps rochika singh apoptosis signal transduction article log restored mitochondrial function mitochondrial complex activity tfeb links autophagy european economic area

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         headline:Enforced lysosomal biogenesis rescues erythromycin- and clindamycin-induced mitochondria-mediated cell death in human cells
         description:Antibiotics are the front-line treatment against many bacterial infectious diseases in human. The excessive and long-term use of antibiotics in human cause several side effects. It is important to understand the underlying molecular mechanisms of action of antibiotics in the host cell to avoid the side effects due to the prevalent uses. In the current study, we investigated the crosstalk between mitochondria and lysosomes in the presence of widely used antibiotics: erythromycin (ERM) and clindamycin (CLDM), which target the 50S subunit of bacterial ribosomes. We report here that both ERM and CLDM induced caspase activation and cell death in several different human cell lines. The activity of the mitochondrial respiratory chain was compromised in the presence of ERM and CLDM leading to bioenergetic crisis and generation of reactive oxygen species. Antibiotics treatment impaired autophagy flux and lysosome numbers, resulting in decreased removal of damaged mitochondria through mitophagy, hence accumulation of defective mitochondria. We further show that over-expression of transcription factor EB (TFEB) increased the lysosome number, restored mitochondrial function and rescued ERM- and CLDM-induced cell death. These studies indicate that antibiotics alter mitochondria and lysosome interactions leading to apoptotsis and may develop a novel approach for targeting inter-organelle crosstalk to limit deleterious antibiotic-induced side effects.
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               type:PostalAddress
            type:Organization
      name:Wang-Xia Wang
      affiliation:
            name:University of Kentucky
            address:
               name:Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
               type:PostalAddress
            type:Organization
            name:University of Kentucky
            address:
               name:Sanders Brown Center on Aging Center, University of Kentucky, Lexington, USA
               type:PostalAddress
            type:Organization
            name:University of Kentucky
            address:
               name:Pathology & Laboratory Medicine, University of Kentucky, Lexington, USA
               type:PostalAddress
            type:Organization
      name:Joe E. Springer
      affiliation:
            name:University of Kentucky
            address:
               name:Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
               type:PostalAddress
            type:Organization
            name:University of Kentucky
            address:
               name:Neuroscience, University of Kentucky, Lexington, USA
               type:PostalAddress
            type:Organization
      name:Rochika Singh
      affiliation:
            name:Indian Institute of Advanced Research
            address:
               name:Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, India
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Rajesh Singh
      affiliation:
            name:The Maharaja Sayajirao University of Baroda
            address:
               name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
      name:Neuroscience, University of Kentucky, Lexington, USA
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
      name:Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
      name:Sanders Brown Center on Aging Center, University of Kentucky, Lexington, USA
      name:Pathology & Laboratory Medicine, University of Kentucky, Lexington, USA
      name:Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, USA
      name:Neuroscience, University of Kentucky, Lexington, USA
      name:Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, India
      name:Department of Bio-Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
WebPageElement:
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