Healthy Mitochondria

Reactive Oxygen Species (ROS) Production Regulated by several factors Regulated by several factors ROS are formed by Oxidative Phosphorylation (ETC) ROS are formed by Oxidative Phosphorylation (ETC) Complexes leak electrons to oxygen, partially reducing the molecule to O -. 2 Complexes leak electrons to oxygen, partially reducing the molecule to O -. 2 Efficiency of Complex I in the ETC Efficiency of Complex I in the ETC Considered the major ROS-generating site in mitochondria Considered the major ROS-generating site in mitochondria In the absence of ADP, electrons derived from Complex II can reversely flow to Complex I, generating increased O -. 2 production In the absence of ADP, electrons derived from Complex II can reversely flow to Complex I, generating increased O -. 2 production

ROS Damage Mitochondria Mitochondria have their own genome Mitochondria have their own genome Human mtDNA lack protective histones and many of the repair mechanisms of the nuclear genome. Human mtDNA lack protective histones and many of the repair mechanisms of the nuclear genome. mtDNA are located proximal to the ROS generating site in the inner membrane. mtDNA are located proximal to the ROS generating site in the inner membrane. Vulnerable to ROS damage Vulnerable to ROS damage

ROS as a Signaling Protein Too much ROS can be damaging to the cell Too much ROS can be damaging to the cell Some ROS formation is necessary Some ROS formation is necessary Induce protective adaptations to stress Induce protective adaptations to stress

Effects of Exercise Exercise will increase ROS production Exercise will increase ROS production The proportion of O 2 that undergoes one electron reduction should decrease with increased ETC activity The proportion of O 2 that undergoes one electron reduction should decrease with increased ETC activity Overall flux of O 2 may increase 10-fold or more above resting levels during exercise Overall flux of O 2 may increase 10-fold or more above resting levels during exercise Increasing the movement of O 2 leads to greater potential to form ROS through the ETC Increasing the movement of O 2 leads to greater potential to form ROS through the ETC

Trained vs. Untrained Mitochondria Untrained: Untrained: Have not adapted to handle the increase O 2 flux Have not adapted to handle the increase O 2 flux Produce more ROS Produce more ROS Trained: Trained: Increased use of the energy pathways Increased use of the energy pathways Have undergone adaptations to handle increase O 2 flux Have undergone adaptations to handle increase O 2 flux Are better able to handle ROS production Are better able to handle ROS production Regular exercise causes adaptation which provide protection against ROS Regular exercise causes adaptation which provide protection against ROS

In Conclusion A healthy mitochondria: A healthy mitochondria: Has not been damaged by ROS Has not been damaged by ROS Has been adapted to handle increases in O 2 flux during exercise Has been adapted to handle increases in O 2 flux during exercise Better use of the energy pathways Better use of the energy pathways Use it or lose it principle Use it or lose it principle The more you use the pathways, the better they function The more you use the pathways, the better they function Less cell death Less cell death More mitochondria to handle stress More mitochondria to handle stress