PT  - JOURNAL ARTICLE
AU  - Nathaniel L. Hepowit
AU  - Eric Blalock
AU  - Sangderk Lee
AU  - Jason A. MacGurn
AU  - Robert C. Dickson
TI  - Myriocin remodels sphingolipids and modulates proteostasis networks to enhance longevity
AID  - 10.1101/2022.05.20.492522
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.20.492522
4099  - http://biorxiv.org/content/early/2022/05/20/2022.05.20.492522.short
4100  - http://biorxiv.org/content/early/2022/05/20/2022.05.20.492522.full
AB  - The increasing elderly population is casting a heavy burden on healthcare due to chronic, age-associated diseases. Nutrient limitation is well known to slow the aging process and improve health. Regrettably, practicing nutrient restriction to improve health is unachievable for most people. Alternatively, pharmacological strategies are being pursued including myriocin which increases lifespan in budding yeast. Myriocin impairs sphingolipid synthesis, resulting in lowered amino acid pools which aid entry into a quiescent, long-live state. Here we present transcriptomic data during 6 h of drug treatment that improve our mechanistic understanding of what myriocin does to promote longevity. Specifically, we present a new role for ubiquitin in longevity. Previously we found that the methionine transporter, Mup1, traffics to the plasma membrane normally in myriocin-treated cells but is not active and is endocytosed sooner than in untreated cells. We now show that Mup1 tagged with a deubiquitinase domain (DUB domain) blocks myriocin-enhanced longevity. Although proteostasis and the role of ubiquitin in it are hallmarks of aging, our finding that deubiquitinating an amino acid transporter is vital for longevity in Myriocin-treated cells is novel. Understanding the role of deubiquitination in longevity has the potential to identify new strategies and targets for promoting healthy aging.Competing Interest StatementThe authors have declared no competing interest.