Research
Interspecies Differences in Proteome Turnover Kinetics Are Correlated With Life Spans and Energetic Demands

https://doi.org/10.1074/mcp.RA120.002301Get rights and content
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Highlights

  • Cross-species proteomic analyses show that turnover is correlated with life span.

  • Correlation between life span and turnover is evident for abundant proteins.

  • Long-lived naked mole rats also have lower ATP production and ROS levels.

  • Despite having slow turnover, naked mole rats tolerate protein misfolding stress.

Abstract

Cells continually degrade and replace damaged proteins. However, the high energetic demand of protein turnover generates reactive oxygen species that compromise the long-term health of the proteome. Thus, the relationship between aging, protein turnover, and energetic demand remains unclear. Here, we used a proteomic approach to measure rates of protein turnover within primary fibroblasts isolated from a number of species with diverse life spans including the longest-lived mammal, the bowhead whale. We show that organismal life span is negatively correlated with turnover rates of highly abundant proteins. In comparison with mice, cells from long-lived naked mole rats have slower rates of protein turnover, lower levels of ATP production, and reduced reactive oxygen species levels. Despite having slower rates of protein turnover, naked mole rat cells tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of a rapid constitutive turnover, long-lived species may have evolved more energetically efficient mechanisms for selective detection and clearance of damaged proteins.

Keywords

Protein turnove
aging
protein degradation
proteostasis
quantitative proteomics

Abbreviations

ACN
acetonitrile
AF
ammonium formate
AGC
automatic gain control
AZC
azetidine-2-carboxylic acid
DMEM
Dulbecco’s modified Eagle’s medium
EMEM
Eagle’s minimum essential medium
ETC
electron transport chain
FBS
fetal bovine serum
GO
gene ontology
H/L
heavy-to-light
iBAQ
intensity-based absolute quantification
LFQ
label-free quantification
OCR
oxygen consumption rate
PER
proton efflux rate
ROS
reactive oxygen species
SILAC
stable isotopic labeling in cell culture
TLS
turnover–life span slope
UPS
ubiquitin–proteasome system

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