The mitochondrial production of reactive oxygen species in relation to aging and pathology.
Mitochondria are known to be strong producers of reactive oxygen species (ROS) and, at the same time, particularly susceptible to the oxidative damage produced by their action on lipids, proteins, and DNA. In particular, damage to mtDNA induces alterations to the polypeptides encoded by mtDNA in the respiratory complexes, with consequent decrease of electron transfer, leading to further production of ROS and thus establishing a vicious circle of oxidative stress and energetic decline. This deficiency in mitochondrial energetic capacity is considered the cause of aging and age-related degenerative diseases. Complex I would be the enzyme most affected by ROS, since it contains seven of the 13 subunits encoded by mtDNA. Accordingly, we found that complex I activity is significantly affected by aging in rat brain and liver mitochondria as well as in human platelets. Moreover, due to its rate control over aerobic respiration, such alterations are reflected on the entire oxidative phosphorylation system. We also investigated the role of mitochondrial complex I in superoxide production and found that the one-electron donor to oxygen is most probably the Fe-S cluster N2. Short chain coenzyme Q (CoQ) analogues enhance ROS formation, presumably by mediating electron transfer from N2 to oxygen, both in bovine heart SMP and in cultured HL60 cells. Nevertheless, we have accumulated much evidence of the antioxidant role of reduced CoQ(10) in several cellular systems and demonstrated the importance of DT-diaphorase and other internal cellular reductases to reduce exogenous CoQ(10) after incorporation.
Genova
Maria Luisa
ML
Dipartimento di Biochimica "G. Moruzzi," University of Bologna, 40126 Bologna, Italy.
Pich
Milena Merlo
MM
Bernacchia
Andrea
A
Bianchi
Cristina
C
Biondi
Annalisa
A
Bovina
Carla
C
Falasca
Anna Ida
AI
Formiggini
Gabriella
G
Castelli
Giovanna Parenti
GP
Lenaz
Giorgio
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D011809:Quinones; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I; D010100:Oxygen