Mitochondrial DNA insertions into nuclear DNA affecting chromosome segregation: Insights for a novel mechanism of immunosenescence in mice

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González Sánchez, Mónica and García Martínez, Víctor and Bravo, Sara and Kobayashi, Hikaru and Martínez de Toda, Irene and González Bermúdez, Blanca and Plaza, Gustavo R. and Fuente del Rey, Mónica de la (2022) Mitochondrial DNA insertions into nuclear DNA affecting chromosome segregation: Insights for a novel mechanism of immunosenescence in mice. Mechanisms of Ageing and Development, 207 (111722). pp. 1-11. ISSN 0047-6374

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Official URL: https://doi.org/10.1016/j.mad.2022.111722



Abstract

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.


Item Type:Article
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CRUE-CSIC (Acuerdos Transformativos 2022)

Uncontrolled Keywords:NUMTs; MtDNAM; Micronuclei; Lymphoproliferation; Immunosenescence; Oxidative stress
Subjects:Medical sciences > Biology > Genetics
ID Code:74580
Deposited On:16 Sep 2022 07:08
Last Modified:16 Sep 2022 08:21

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