RT Journal Article
T1 Mitochondrial DNA insertions into nuclear DNA affecting chromosome segregation: Insights for a novel mechanism of immunosenescence in mice
A1 González Sánchez, Mónica
A1 García Martínez, Víctor
A1 Bravo, Sara
A1 Kobayashi, Hikaru
A1 Martínez de Toda, Irene
A1 González Bermúdez, Blanca
A1 Plaza, Gustavo R.
A1 Fuente del Rey, Mónica de la
AB Mitochondrial DNA sequences were found inserted in the nuclear genome of mouse peritoneal T lymphocytes that increased progressively with aging. These insertions were preferentially located at the pericentromeric heterochromatin. In the same individuals, binucleated T-cells with micronuclei showed a significantly increased frequency associated with age. Most of them were positive for centromere sequences, reflecting the loss of chromatids or whole chromosomes. The proliferative capacity of T lymphocytes decreased with age as well as the glutathione reductase activity, whereas the oxidized glutathione and malondialdehyde concentrations exhibited a significant increase. These results may point to a common process that provides insights for a new approach to understanding immunosenescence. We propose a novel mechanism in which mitochondrial fragments, originated by the increased oxidative stress status during aging, accumulate inside the nuclear genome of T lymphocytes in a timedependent way. The primary entrance of mitochondrial fragments at the pericentromeric regions may compromise chromosome segregation, causing genetic loss that leads to micronuclei formation, rendering aneuploid cells with reduced proliferation capacity, one of the hallmark of immunosenescence. Future experiments deciphering the mechanistic basis of this phenomenon are needed.
PB Elsevier
SN 0047-6374
YR 2022
FD 2022-08-09
LK https://hdl.handle.net/20.500.14352/71980
UL https://hdl.handle.net/20.500.14352/71980
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2022)
NO Ministerio de Economía y Competitividad (MINECO)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 6 abr 2025