Telomerase and mTOR in the brain: the mitochondria connection

Abstract

Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well. We have recently published that TERT protein accumulated in mitochondria from brain tissue of mice that have undergone short-term dietary restriction (DR) and rapamycin treatment. This localization correlated to lower levels of oxidative stress in these brain mitochondria. Since rapamycin treatment decreases mTOR signaling which is also thought to play an important role for the beneficial effects of DR, we conclude that the mTOR pathway might be involved in the TERT localization and its effects in brain mitochondria in vivo. These data are in line with previous findings from our group about increased mitochondrial localization of TERT in Alzheimer's disease (AD) brains and a protective function of TERT protein in neurons in vitro against pathological tau.

Keywords

• telomerase; brain; neuron; mitochondria; mTOR; ROS; dietary restriction; rapamycin