RT Journal Article
SR Electronic
T1 Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondria
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202302127
DO 10.26508/lsa.202302127
VO 6
IS 9
A1 Kim, Jun Yong
A1 Atanassov, Ilian
A1 Dethloff, Frederik
A1 Kroczek, Lara
A1 Langer, Thomas
YR 2023
UL https://www.life-science-alliance.org/content/6/9/e202302127.abstract
AB Mitochondrial dysfunction and cellular senescence are hallmarks of aging. However, the relationship between these two phenomena remains incompletely understood. In this study, we investigated the rewiring of mitochondria upon development of the senescent state in human IMR90 fibroblasts. Determining the bioenergetic activities and abundance of mitochondria, we demonstrate that senescent cells accumulate mitochondria with reduced OXPHOS activity, resulting in an overall increase of mitochondrial activities in senescent cells. Time-resolved proteomic analyses revealed extensive reprogramming of the mitochondrial proteome upon senescence development and allowed the identification of metabolic pathways that are rewired with different kinetics upon establishment of the senescent state. Among the early responding pathways, the degradation of branched-chain amino acid was increased, whereas the one carbon folate metabolism was decreased. Late-responding pathways include lipid metabolism and mitochondrial translation. These signatures were confirmed by metabolic flux analyses, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence. Together, our data provide a comprehensive view on the changes in mitochondrial proteome in senescent cells and reveal how the mitochondrial metabolism is rewired in senescent cells.