Mammalian Fibroblast Turnover Rates, Protein Abundance, and Protein Damage Response

ABSTRACT: Within a cell, proteins are in a dynamic state of turnover and are continuously synthesized and degraded. As an energetically expensive cellular process, protein turnover can have two opposing effects on maintaining a healthy proteome during the lifespan of an organism. Rapid protein turnover can replace old and damaged proteins with newly synthesized proteins. However, the high energetic demands of this process can potentially generate damaging reactive oxygen species that comprise the long-term health of the proteome. Thus, the relationship between aging, protein turnover kinetics and energetic demands of an organism remain unclear. Here, we used a proteomic approach to measure global rates of protein turnover within cultured fibroblasts isolated from a number of species with a wide range of lifespans. We show that organismal lifespan is negatively correlated with global rates of turnover. By further comparing cells from mice and naked mole rats (a short-lived and long-lived rodent species, respectively) we show that the latter has slower rates of turnover, lower levels of ATP production and reduced cellular ROS levels. Despite its slower rate of protein turnover, naked mole rat cells are able to tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive protein turnover, long-lived species such as the naked mole rat have may have evolved more energetically efficient mechanisms for selective clearance of damaged proteins.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Bos Taurus (bovine)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Kyle Swovick  

LAB HEAD: Sina Ghaemmaghami

PROVIDER: PXD018325 | Pride | 2020-05-07

REPOSITORIES: Pride