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Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria

Lookup NU author(s): Dr Satomi Miwa, Dr Rafal Czapiewski, Tengfei Wan, Amy Bell, Kirsten Hill, Professor Thomas von Zglinicki, Dr Gabriele Saretzki

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/-mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.


Publication metadata

Author(s): Miwa S, Czapiewski R, Wan TF, Bell A, Hill KN, von Zglinicki T, Saretzki G

Publication type: Article

Publication status: Published

Journal: Aging

Year: 2016

Volume: 8

Issue: 10

Pages: 2551-2567

Online publication date: 22/10/2016

Acceptance date: 02/10/2016

Date deposited: 10/05/2017

ISSN (print): 1945-4589

Publisher: Impact Journal LLC

URL: http://dx.doi.org/10.18632/aging.101089

DOI: 10.18632/aging.101089


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