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Aging, Metabolism, Stress, Pathogenesis, and Small RNAs in C. elegans Topic Meeting 2012
LC-MS Proteomics Analysis Reveals Both Common and Unique
Changes in the Proteome of Insulin/IGF-1 Receptor Mutant and
Dietary Restricted C. elegans
Geert Depuydt1 , Fang Xie2 , Vladislav Petyuk2 , Heather Brewer2 , Arne Smolders1 , Ineke
Dhondt1 , Nilesh Shanmugam1 , David Camp II2 , Richard Smith2 , Bart Braeckman2 1 2 Biology Department, Ghent University, B-9000 Ghent, Belgium, Biological
Sciences Division and Environmental Molecular Sciences Laboratory, Pacific
Northwest National Laboratory, Richland, WA 99352, USA
Impaired insulin/IGF-1 signaling (IIS) and dietary restriction are two well-characterized
lifespan extending interventions that operate by (partially) independent mechanisms in C.
elegans. Taking advantage of recent developments in quantitative LC-MS/MS based proteomics,
we sought to uncover potentially universal, as well as condition-specific, proteomic changes
that could underlie daf-2(e1370)- and dietary restriction-induced longevity. A most striking
pattern in the proteome fingerprints of both long-lived IIS-mutant and DR worms is the overall
decrease in the abundance of a large number of ribosomal proteins of both the large (60S)
and small (40S) subunits. Consistently, we found decreased rates of protein synthesis in our
long-lived worms. These results indicate that a general downregulation in mRNA translation
rate is part of an adaptive response that allows daf-2 and DR worms to be long-lived. A second
common pattern in these worms is the increased abundance of many muscle proteins, which
we could attribute to an increase in relative, but not absolute, muscle biomass. In addition,
increased mRNA levels of muscle-related genes and higher concentrations of branched-chain
amino acids as a result of their reduced catabolism in daf-2, suggest C. elegans attempts
to preserve muscle integrity in conditions of low nutrient availability. A most striking pattern
in the daf-2 proteome profile is the strong upregulation of most core intermediary metabolic
pathways (e.g. carbohydrate, fat, oxidative ATP generation), including several pathways that
are reciprocally regulated. Despite this upregulation of the energy metabolic machinery, we
found daf-2 animals fit a hypometabolic energy profile, similar to dauers, but retain the ability
for strong activity bursts when necessary.
Contact: Geert.Depuydt@ugent.be
Lab: Braeckman
8
Session 2