Mitochondrial ROS

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Production of mitochondrial ROS, mitochondrial ROS

Mitochondrial ROS (mtROS or mROS) are reactive oxygen species (ROS) that are produced by mitochondria.[1][2] Generation of mitochondrial ROS mainly takes place at the electron transport chain located on the inner mitochondrial membrane during the process of oxidative phosphorylation (OXPHOS). Leakage of electrons at complex I and complex III from electron transport chains leads to partial reduction of oxygen to form superoxide. Subsequently, superoxide is quickly dismutated to hydrogen peroxide by two dismutases including superoxide dismutase 2 (SOD2) in mitochondrial matrix and superoxide dismutase 1 (SOD1) in mitochondrial intermembrane space. Collectively, both superoxide and hydrogen peroxide generated in this process are considered as mitochondrial ROS.[3]

Once thought as merely the by-products of cellular metabolism, mitochondrial ROS are increasingly viewed as important signaling molecules,[4] whose levels of generation at 11 currently-identified sites vary depending on cellular energy supply and demand.[5][6] At low levels, mitochondrial ROS are considered to be important for metabolic adaptation as seen in hypoxia. Mitochondrial ROS, stimulated by danger signals such as lysophosphatidylcholine and Toll-like receptor 4 and Toll-like receptor 2 bacterial ligands lipopolysaccharide (LPS) and lipopeptides, are involved in regulating inflammatory response. Finally, high levels of mitochondrial ROS activate apoptosis/autophagy pathways capable of inducing cell death.[7][8][9]


Mitochondrial ROS can promote cellular senescence and aging phenotypes in the skin of mice.[10] Ordinarily mitochondrial SOD2 protects against mitochondrial ROS. Epidermal cells in mutant mice with a genetic SOD2 deficiency undergo cellular senescence, nuclear DNA damage, and irreversible arrest of proliferation in a portion of their keratinocytes.[10][11]

Mutant mice with a conditional deficiency for mitochondrial SOD2 in connective tissue have an accelerated aging phenotype.[12] This aging phenotype includes weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis, muscle degeneration and reduced life span.

DNA damage[edit]

Mitochondrial ROS attack DNA readily, generating a variety of DNA damages such as oxidized bases and strand breaks. The major mechanism that cells use to repair oxidized bases such as 8-hydroxyguanine, formamidopyrimidine and 5-hydroxyuracil is base excision repair (BER).[13] BER occurs in both the cell nucleus and in mitochondria.


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  5. ^ Trewin, Adam J.; Parker, Lewan; Shaw, Christopher S.; Hiam, Danielle S.; Garnham, Andrew; Levinger, Itamar; McConell, Glenn K.; Stepto, Nigel K. (November 2018). "Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H 2 O 2 release, respiration, and cell signaling as endurance exercise even with less work". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 315 (5): R1003–R1016. doi:10.1152/ajpregu.00096.2018. ISSN 0363-6119.
  6. ^ Goncalves, Renata L. S.; Quinlan, Casey L.; Perevoshchikova, Irina V.; Hey-Mogensen, Martin; Brand, Martin D. (2015-01-02). "Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise". Journal of Biological Chemistry. 290 (1): 209–227. doi:10.1074/jbc.M114.619072. ISSN 0021-9258. PMC 4281723.
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  9. ^ West AP (April 2011). "TLR signalling augments macrophage bactericidal activity through mitochondrial ROS". Nature. 472 (7344): 476–480. doi:10.1038/nature09973. PMC 3460538. PMID 21525932.
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