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SUMMARY:Cellular Responses to Mitochondrial Dysfunction - Professor Anna W
 redenberg\, Karolinska Institute\, Stockholm\, Sweden
DTSTART:20250516T140000Z
DTEND:20250516T150000Z
UID:TALK227776@talks.cam.ac.uk
CONTACT:Lisa Arnold
DESCRIPTION:Mitochondrial dysfunction is a hallmark of numerous human dise
 ases and is often accompanied by changes in metabolic flux\, mitochondrial
  morphology\, and proteostatic signalling. In patients\, such dysfunction 
 is associated with conserved adaptive responses involving proteome remodel
 ing\, altered autophagy\, and disruption of mitochondrial one-carbon metab
 olism. While many of these changes act as compensatory mechanisms\, their 
 chronic activation may ultimately impair cellular function.\nTo identify m
 odifiers of mitochondrial genome instability\, we performed a genetic scre
 en in Drosophila melanogaster expressing a proofreading-deficient mtDNA po
 lymerase (POLγexo-). We identified critical pathways involved in nutrient
  sensing\, insulin signalling\, mitochondrial protein import\, and autopha
 gy that rescue the lethal phenotype of POLγexo- flies. Notably\, hemizygo
 sity for dilp1\, atg2\, tim14\, or melted restored autophagic flux and pro
 teasome activity\, and supported metabolic adaptation. While mtDNA mutatio
 n frequencies remained high in most rescued lines\, melted-rescued flies s
 howed a reduction\, suggesting early developmental action. Our findings fu
 rther identify the nucleation step of autophagy as a key therapeutic targe
 t in mitigating mitochondrial genome instability.
LOCATION:MRC MBU\, Level 3 Seminar\, The Keith Peters Building\, CB2 0XY
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