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SUMMARY:External Seminar - Louis Lapierre "Spatial regulation of proteosta
 sis during aging in Caenorhabditis elegans"
DTSTART:20261016T090000Z
DTEND:20261016T103000Z
DTSTAMP:20260927T222400Z
UID:indico-event-401@indico.i2bc.paris-saclay.fr
DESCRIPTION:Spatial regulation of proteostasis during aging in Caenorhabdi
 tis elegans\nLouis Lapierre\nUniversité de MonctonMoncton\, NB\, Canada\n
 \nSummary:\nProtein homeostasis (proteostasis) is essential for maintainin
 g cellular function and preventing the accumulation of damaged and misfold
 ed proteins during aging. Although proteostasis is traditionally viewed as
  a balance between protein synthesis\, folding\, and degradation\, emergin
 g evidence indicates that the spatial organization and partitioning of pro
 teins and proteostatic machinery across subcellular compartments and tissu
 es are equally important determinants of proteome integrity. Using Caenorh
 abditis elegans\, our work investigates how spatially regulated proteostat
 ic mechanisms contribute to protein quality control and longevity.By exami
 ning the regulatory network of the selective autophagy receptor SQST-1/SQS
 TM1\, we uncovered a role for subcellular protein partitioning in autophag
 ic flux and identified lipid droplets as an unexpected proteostatic compar
 tment. Unbiased genome-wide RNAi screening for SQST-1/SQSTM1 revealed that
  lipid droplet-associated proteins modulate proteostasis. Increasing intes
 tinal lipid droplets through inhibition of atgl-1/ATGL promoted autophagy\
 , facilitated the accumulation and handling of ubiquitinated proteins\, an
 d extended lifespan. Conversely\, reducing lipid droplets exacerbated prot
 eostatic collapse and shortened the lifespan of long-lived daf-2 animals\,
  establishing lipid droplets as important spatial mediators of proteostasi
 s and longevity.  We also investigated how proteostatic burden is distrib
 uted across tissues during aging. Validation of commonly used tissue-speci
 fic RNAi systems revealed substantial and temperature-dependent difference
 s in RNAi sensitivity among rde-1 and sid-1 mutant backgrounds\, highlight
 ing important considerations for interpreting tissue-specific RNAi studies
 . Using validated systems\, we found that proteasomal burden differs marke
 dly between the germline and soma\, with age-dependent accumulation of vit
 ellogenin proteins contributing substantially to polyubiquitinated protein
  levels in the gonad. Unexpectedly\, we further found that the polyubiquit
 in gene ubq-1 is required for transcription of highly expressed genes\, in
 cluding vitellogenins\, revealing a broader role for ubiquitin beyond prot
 ein degradation.Taken together\, these findings demonstrate that proteosta
 sis during aging is regulated across multiple spatial scales—from subcel
 lular compartments to individual tissues—and that these spatially organi
 zed mechanisms are tightly linked to organismal longevity. Our work highli
 ghts protein partitioning\, lipid droplets\, autophagy\, proteasomal funct
 ion\, and tissue-specific proteostatic burden as interconnected determinan
 ts of proteome maintenance during aging\, providing new avenues for unders
 tanding and modulating age-associated proteostatic decline.\n \nInvité p
 ar Audrey Esclatine (audrey.esclatine@i2bc.paris-saclay.fr)\n\nhttps://ind
 ico.i2bc.paris-saclay.fr/event/401/
LOCATION:B22-N0-001 - Salle de Conférences (I2BC CNRS Gif)
URL:https://indico.i2bc.paris-saclay.fr/event/401/
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