In vivo regulation of mitochondrial ROS levels as a strategy to extend lifespan.
Alberto Sanz
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
E-mail: [email protected]
Mitochondrial Reactive Oxygen Species (ROS) can cause oxidative damage and subsequently cell death. However, ROS are also essential messengers implicated in cellular signaling and therefore required to maintain homeostasis. It is usually accepted that their role as damaging or signaling agents is determined by their concentration. Here, I will discuss that where and how ROS are produced is as important as the amount of ROS to determine their physiological effects. For example, Drosophila ageing is characterized by the accumulation of damaged mitochondria and high levels of ROS. However, inducing high levels of ROS specifically stimulating reverse electron transport (RET) through respiratory complex I (CI) extends lifespan and protects mitochondrial function during ageing. On the other hand, knock-down of Sod2 increases superoxide levels, reduces mitochondrial respiration and dramatically shortens lifespan. Paradoxically, inducing RET protects mitochondrial function and rescues lifespan in spite of increasing total ROS levels. This indicates that the RET-ROS signaling is specifically recognized and activates mechanisms of protection. The ability of RET to modify the rate of ageing highlights a potential physiological role and the opportunity to delay ageing and age-related diseases through changes in the redox state of the CoQ pool that will induce RET in vivo.
Financial interest disclosure: none to declare.
Alberto Sanz
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
E-mail: [email protected]
Mitochondrial Reactive Oxygen Species (ROS) can cause oxidative damage and subsequently cell death. However, ROS are also essential messengers implicated in cellular signaling and therefore required to maintain homeostasis. It is usually accepted that their role as damaging or signaling agents is determined by their concentration. Here, I will discuss that where and how ROS are produced is as important as the amount of ROS to determine their physiological effects. For example, Drosophila ageing is characterized by the accumulation of damaged mitochondria and high levels of ROS. However, inducing high levels of ROS specifically stimulating reverse electron transport (RET) through respiratory complex I (CI) extends lifespan and protects mitochondrial function during ageing. On the other hand, knock-down of Sod2 increases superoxide levels, reduces mitochondrial respiration and dramatically shortens lifespan. Paradoxically, inducing RET protects mitochondrial function and rescues lifespan in spite of increasing total ROS levels. This indicates that the RET-ROS signaling is specifically recognized and activates mechanisms of protection. The ability of RET to modify the rate of ageing highlights a potential physiological role and the opportunity to delay ageing and age-related diseases through changes in the redox state of the CoQ pool that will induce RET in vivo.
Financial interest disclosure: none to declare.
