2020
DOI: 10.1073/pnas.1916414117
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Abstract: The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is electrophoretically transported by the ATP/ADP antiporter to the catalytic site of bound hexokinase or bound creatine kinase without ATP dilution … Show more

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Cited by 122 publications
(82 citation statements)
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“…It has long been known that a mild depolarization of the mitochondrial inner membrane inhibits mitochondrial ROS production [ 7 ]. This is one way through which the post-translational control of mitochondrial uncoupling proteins UCP2 and UCP3 by glutathionylation may decrease mitochondrial ROS production [ 8 , 9 ]. Recent evidence supports the idea that mild mitochondrial depolarization is crucial for the slowing of aging processes associated with oxidative damage [ 8 ].…”
Section: Ros Generation and Signalingmentioning
confidence: 99%
See 1 more Smart Citation
“…It has long been known that a mild depolarization of the mitochondrial inner membrane inhibits mitochondrial ROS production [ 7 ]. This is one way through which the post-translational control of mitochondrial uncoupling proteins UCP2 and UCP3 by glutathionylation may decrease mitochondrial ROS production [ 8 , 9 ]. Recent evidence supports the idea that mild mitochondrial depolarization is crucial for the slowing of aging processes associated with oxidative damage [ 8 ].…”
Section: Ros Generation and Signalingmentioning
confidence: 99%
“…Several in-depth reviews have been published on the molecular mechanisms of GPXs regulation in tumors and their function in different stages of tumor progression [ 115 , 116 , 117 ]. GPX1 and 2 are highly expressed in the gastrointestinal epithelium and have been implicated in the development and promotion of colorectal cancer [ 8 ]. For instance, mice deficient in both GPX1 and GPX2 genes, spontaneously developed ileocolitis at a young age.…”
Section: Glutathione Inflammation and Cancermentioning
confidence: 99%
“…For instance mitochondria from the long lived naked mole rat (NMR) produce less ROS than comparable shorter lived animals [ 139 , 140 ]. Furthermore the mitochondria in NMR, and bats, also appear to be able to maintain a depolarisation of the inner membrane for much longer during their life cycle, which is a key mechanism to reduce ROS production during ageing [ 141 ]. A key idea that relates to this is the Redox-Optimised ROS Balance (R-ORB) hypothesis, which stipulates that mitochondrial emission of ROS will reach a nadir when respiratory rate reaches a maximum – in effect, mitochondria will maximise ATP production and minimise ROS as they evolved to work at an intermediate redox state [ 142 , 143 ].…”
Section: The Immune System Hormesis and Mitochondriamentioning
confidence: 99%
“…In this context, the proposed MNs may be the safest triad for mild mitochondrial effects. Lipoic acid can directly scavenge superoxide and improve mitochondrial function [ 130 ], CoQ10 is an important endogenous lipid-soluble antioxidant [ 131 ], and CARN reduces OS in many biological systems [ 132 , 133 ]. Despite the fact that the components of the MN triad are safe for use in clinical trials and have been studied for their ability to decelerate the aging of different organisms, their effectiveness will most likely depend on the selection of the optimal doses and on the time of their administration.…”
Section: Aging Antioxidants and Possible Advantages Of The Mn “Tmentioning
confidence: 99%