US EPA

1559186 

Journal Article 

How mitochondria produce reactive oxygen species 

Murphy, MP 

2009 

Yes 

Biochemical Journal
ISSN: 0264-6021
EISSN: 1470-8728 

417 

1-13 

19061483 

10.1042/BJ20081386 

WOS:000262230700001 

The production of ROS (reactive oxygen species) by mammalian
mitochondria is important because it underlies oxidative damage in many pathologies and
contributes to retrograde redox signalling from the organelle to the cytosol and nucleus.
Superoxide (O(2)(center dot-)) is the proximal mitochondrial ROS, and in the present review 1
outline the principles that govern O(2)(center dot-)production within the matrix of mammalian
mitochondria. The flux of O(2)(center dot-) is related to the concentration of potential electron
donors, the local concentration of O(2)(center dot-) and the second-order rate constants for the
reactions between them. Two modes of operation by isolated mitochondria result in significant O
(2)(center dot-) production, predominantly from complex I: (i) when the mitochondria are not
making ATP and consequently have a high Delta p (protonmotive force) and a reduced CoQ (coenzyme
Q) pool; and (ii) when there is it high NADH/NAD(+) ratio in the mitochondrial matrix. For
mitochondria that are actively making ATP, and consequently have a lower Delta p and NADH/NAD(+)
ratio, the extent of O(2)(center dot-) production is far lower. The generation of O(2)(center
dot-) within the mitochondrial matrix depends critically on Delta p, the NADH/NAD(+) and CoQH
(2)/CoQ ratios and the local O(2)(center dot-) concentration, which are all highly variable and
difficult to measure in vivo. Consequently, it is not possible to estimate O(2)(center dot-)
generation by mitochondria in vivo from O(2)(center dot-) production rates by isolated
mitochondria, and such extrapolations in the literature are misleading. Even so, the description
outlined here facilitates the understanding of factors that favour mitochondrial ROS production.
There is a clear need to develop better methods to Measure mitochondrial O(2)(center dot-) and H
(2)O(2) formation in vivo,as uncertainty about these values hampers studies oil the role of
mitochondrial ROS in pathological oxidative damage and redox signalling. 

complex I; hydrogen peroxide; mitochondrion; reactive oxygen species (ROS); respiratory chain; Superoxide