PT - JOURNAL ARTICLE AU - Chen Liu AU - Ioannis H. Hatzianestis AU - Thorsten Pfirrmann AU - Salim H. Reza AU - Elena A. Minina AU - Ali Moazzami AU - Simon Stael AU - Emilio Gutierrez-Beltran AU - Evgenia Pitsili AU - Peter Dörmann AU - Sabine D’ Andrea AU - Kris Gevaert AU - Francisco Romero-Campero AU - Pingtao Ding AU - Moritz K. Nowack AU - Frank Van Breusegem AU - Jonathan D. G. Jones AU - Peter V Bozhkov AU - Panagiotis N. Moschou TI - Seed Longevity is Controlled by Metacaspases AID - 10.1101/2023.03.19.533321 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.19.533321 4099 - http://biorxiv.org/content/early/2023/03/20/2023.03.19.533321.short 4100 - http://biorxiv.org/content/early/2023/03/20/2023.03.19.533321.full AB - To survive extreme desiccation, seeds enter dormancy that can last millennia. This dormancy involves the accumulation of protective but structurally disordered storage proteins through unknown adjustments of proteolytic surveillance mechanisms. Mutation of all six types II metacaspases (MCAs)-II in the model plant Arabidopsis revealed their essential role in modulating these proteolytic mechanisms. MCA-II mutant seeds fail to properly target at the endoplasmic reticulum (ER) the AAA ATPase Cell Division Cycle 48 (CDC48) to dispose of misfolded proteins. MCA-IIs cleave a CDC48 adaptor, the ubiquitination regulatory X domain-containing (PUX) responsible for localizing CDC48 to the lipid droplets. When cleaved, CDC48-PUX is inactivated and allows a lipid droplet-to-ER shuttling of CDC48, an important step in the regulation of seeds’ lifespan. In sum, we uncover antagonism between proteolytic pathways bestowing longevity.One-Sentence Summary Metacaspase proteases confer seed longevity by antagonizing CDC48 activity.Competing Interest StatementThe authors have declared no competing interest.