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http://hdl.handle.net/2080/3936
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DC Field | Value | Language |
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dc.contributor.author | Patra, Srimanta | - |
dc.contributor.author | Bhutia, Sujit Kumar | - |
dc.date.accessioned | 2023-01-24T12:52:04Z | - |
dc.date.available | 2023-01-24T12:52:04Z | - |
dc.date.issued | 2023-01 | - |
dc.identifier.citation | 42nd Annual Conference of IACR (IACR 2023), ACTREC, Mumbai, 12-15 January 2023 | en_US |
dc.identifier.uri | http://hdl.handle.net/2080/3936 | - |
dc.description | Copyright belongs to proceeding publisher | en_US |
dc.description.abstract | Distinct mitochondrial fission parameters predict cancer cell survival and death owing to their fission site. Symmetric fission leads to cell survival with subsequent mitochondrial biogenesis; while, asymmetric fission leads to mitophagic clearance of dysfunctional mitochondria. The present study unveils imperative molecular regulation of SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III HDAC as a critical controller of asymmetric mitochondrial fission. Gallic acid (GA), a small molecule activator of SIRT1, primarily induces DNM1Lmediated mitochondrial fission and perinuclear clustering with a subsequent decrease in the expression of RHOT1. Further, GA induced SIRT1 activation directs FIS1 recruitment to the asymmetric fission sites to the mitochondrial daughter filaments having low mitochondrial membrane permeability, higher mitochondrial superoxide, low mtDNA content, and high calcium efflux. In addition, our data showed that parkin was recruited to the asymmetrically fissioned mitochondrial sub-population to be engulfed by mitophagy. Mechanistically, the nuclear translocation of SIRT1 after gallic acid treatment redirects deacetylated LC3 from the nucleus to the cytoplasm to induce autophagy. Further, the induction of mitophagy followed by asymmetric mitochondrial fission is SIRT1 dependent as inhibition of SIRT1 blocks mitochondrial fission and mitophagy. Furthermore, GA impairs autophagic flux through decreased expression of RAB7A and its recruitment to lysosome and autophagosome. The subsequent accumulation of mitophagosome enhances generation of mitochondrial superoxide leading to apoptotic cell death in oral cancer cells. | en_US |
dc.subject | Gallic acid | en_US |
dc.subject | SIRT1 activation | en_US |
dc.subject | asymmetric mitochondrial fission | en_US |
dc.title | Gallic Acid Mediated SIRT1 Activation Directs Asymmetric Mitochondrial Fission Followed by Mitophagic Flux Inhibition to Induce Apoptotic Cell Death | en_US |
dc.type | Presentation | en_US |
Appears in Collections: | Conference Papers |
Files in This Item:
File | Description | Size | Format | |
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2023_IACR_SPatra_Gallic.pdf | Poster | 1.69 MB | Adobe PDF | View/Open |
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