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The role of succinate dehydrogenase (SDH) in the hypoxia tolerance of naked mole-rats (Heterocephalus glaber)

Grant number: 19/26391-2
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2020
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal researcher:Aníbal Eugênio Vercesi
Grantee:Marina Rincon Sartori
Supervisor abroad: Matthew Pamenter
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of Ottawa (uOttawa), Canada  
Associated to the scholarship:17/05487-6 - Mitochondrial function and molecular markers associated with aging in the long-lived red-footed tortoise Chelonoidis carbonaria, BP.PD

Abstract

Succinate dehydrogenase (SDH), also known as complex II of the mitochondrial respiratory chain, perform a number of functions beyond the transfer of electrons. One such function is its participation in ischemic preconditioning, as SDH is involved in the succinate accumulation that occurs during ischemia reperfusion (IR). IR invokes tissue injury and inflammation driven by reactive oxygen species (ROS) generation and opening of the mitochondrial permeability transition pore (mPTP) during reoxygenation. Succinate accumulation has been implicated in the generation of ROS during IR, however its role in IR injury is unresolved. In contrast to the majority of mammals, a hypoxia-tolerant species, the naked-mole rat (Heterocephalus glaber), can survive long periods of hypoxia without apparent deleterious effects. Despite few studies, evidence suggests that hypoxia tolerant species may accumulate lower levels of succinate and present a modified succinate metabolism as adaptations to cope with their hypoxic environments. In order to understand this mechanism of hypoxia tolerance we propose to investigate the succinate-driven bioenergetics of naked mole-rats. Specifically, we aim to compare mitochondrial respiration rates, ROS generation, mPTP susceptibility and mitochondrial dynamics in normoxia, hypoxia and following hypoxia-reoxygenation. Naked mole-rat adaptations can offer valuable insights into novel treatments against pathologies related to low oxygen stress, such as stroke and heart attack. (AU)

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