Please use this identifier to cite or link to this item: http://hdl.handle.net/2080/3919
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dc.contributor.authorPraharaj, Prakash P.-
dc.contributor.authorBhutia, Sujit Kumar-
dc.date.accessioned2023-01-18T04:39:00Z-
dc.date.available2023-01-18T04:39:00Z-
dc.date.issued2023-01-
dc.identifier.citation42nd Annual Conference of IACR (IACR 2023), ACTREC, Mumbai, 12-15 January 2023en_US
dc.identifier.urihttp://hdl.handle.net/2080/3919-
dc.descriptionCopyright belongs to proceeding publisheren_US
dc.description.abstractMitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU coordinately interacts with BAX and LC3 forming a tri-complex to clear damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes causing reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral canceren_US
dc.subjectClusterinen_US
dc.subjectmitochondrial biogenesisen_US
dc.subjectmitophagyen_US
dc.subjectmitophagy-associated cell deathen_US
dc.subjectPPARGC1A/PGC1αen_US
dc.titleCLU (clusterin) and PPARGC1A/PGC1α Coordinately Control Mitophagy and Mitochondrial Biogenesis for Oral Cancer Cell Survivalen_US
dc.typeArticleen_US
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