Intact mitochondrial function in the setting of telomere-induced senescence

Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven...

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Bibliographic Details
Published in:Aging cell 2023-10, Vol.22 (10), p.e13941-e13941
Main Authors: Sullivan, Daniel I, Bello, Fiona M, Silva, Agustin Gil, Redding, Kevin M, Giordano, Luca, Hinchie, Angela M, Loughridge, Kelly E, Mora, Ana L, Königshoff, Melanie, Kaufman, Brett A, Jurczak, Michael J, Alder, Jonathan K
Format: Article
Language:English
Subjects:
Antibodies
Cell cycle
Cellular Senescence - genetics
DNA damage
Embryos
Fibroblasts
Fibroblasts - metabolism
Gene expression
Hepatocytes
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Proteins
Senescence
Telomere - genetics
Telomere-binding protein
Telomere-Binding Proteins - metabolism
TRF2 protein
Yeast
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Summary:Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere-binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence, which may facilitate continued cellular functions.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.13941