MSc Exit Seminar- Gabriele Nandal

MSc Exit Seminar

Friday, July 19^th, 2019 at 10:10am – Ramsay Wright Building, Room 432

Gabriele Nandal (Buck Lab)

Characterization of Sirtuin 3 and Targets in the Western Painted Turtle

The western painted turtle (Chrysemys picta) is a champion anaerobe capable of surviving months with little to no oxygen. This species’ anoxia tolerance is enabled by many physiological and biochemical adaptations; metabolic depression is perhaps one of the most useful mechanisms that enables the turtle’s survival. In response to anoxia the turtle can suppress its metabolic rate by 90%, this tolerance is partly achieved through downregulation of both protein synthesis and activity in order to minimize ATP demand. Cellular functioning can then be modulated through an ATP-inexpensive, reversible, and rapid post-translational protein modifications. Cellular metabolism is highly regulated by reversible-acetylation of the mitochondrial proteome, however it is relatively unexamined in the anoxia-tolerant turtle. In the mitochondria, Sirtuin 3 (SIRT3) is the global deacetylase, and is involved in many cellular processes such as metabolic regulation and stress resistance. This thesis shows that while the turtle exhibited increases mitochondrial acetylation during early anoxia in the brain and liver, concomitantly SIRT3 protein levels were also elevated. In addition, Cyclophilin D levels, a direct target of SIRT3, were also shown to be elevated during anoxia. Another target of SIRT3, p65 subunit of NF-kB exhibited increased deacetylation during anoxia and reoxygenation in the brain. While no difference in prevalence or activity of manganese superoxide dismutase, an antioxidant target of SIRT3, was observed either during anoxia or reoxygenation. Overall, this thesis provides the first evidence that SIRT3 and mitochondrial proteome acetylation may play a role in the regulation of anoxia in the painted turtle.