Thread by @TuckerGoodrich

"Removal of these CL [cardiolipin] decreases electron-transport activity by ~50% and completely inhibits proton translocation..."

@HyperlipidM

"Peroxidized CL is also much more effective than either H2O2, or tert-BOOH for inactivation, or chemical modification of CcO. [100- to a 1000-fold] less CLOOH are required to modify the CcO subunits than is required for H2O2 or tert-BOOH to modify CcO to a similar extent."

"Because CL is more susceptible to peroxidation than other PLs, CL is expected to be the major source of HNE and MDA within the inner mitochondrial membrane, although this may not be necessarily true for protein bound CL."

"Reactive aldehydes are known to inactivate the electron transfer complexes. For example, exposure of purified detergent-solubilized CcO [Cytochrome c Oxidase] to an excess of HNE decreases electron transport activity by as much as 50% [64]."

@BenBikmanPhD

"Inactivation is dependent upon the HNE concentration and follows pseudo-first-order kinetics. Six CcO subunits (II, IV, Vb, VIIa, VIIc & VIII) are chemically modifi ed after exposure of CcO to 0.1 – 0.5 mM HNE."

"HNE mediated alteration of CcO function also occurs during ischemia/reperfusion of rat hearts with a decrease in CcO activity (59% of control) that correlates with increased mitochondrial HNE concentration and generation of HNE adducts within CcO subunit IV [67]."

"Furthermore, inhibition of CcO by HNE is
not always observed. ...exposure of isolated subsarcolemmal rat heart mito. to a relatively high conc. of HNE, 50 μ M HNE for 5 minutes does not alter CcO activity although inactivation of... pyruvate dehydrogenase
does occur."

"This hypothesis that lipid-derived aldehydes may be deleterious to cyt bc1 [complex III]
has been verified by exposing brain mitochondria to a concentration of HNE comparable to that occurring in patients with Alzheimer’s disease."

@TuitNutrition @BenBikmanPhD

"Cyt bc1 was found to be the respiratory complex most susceptible to HNE, with approximately 70% loss of activity [109]."

"At present, there is no evidence that cyt bc1 is affected by exposure to MDA, at least in situ."

"Moreover, ROS-induced modification of complex I is believed to initiate or contribute to many pathological conditions including Parkinson's and other neurodegenerative diseases, ischemia/reperfusion injury, atherosclerosis, and overall aging [123 – 125]."

"However, the direct effect of HNE-adduct formation on complex I activity has not been demonstrated [70]."

"Susceptibility of mitochondrial electron-transport complexes to oxidative damage. Focus on cytochrome c oxidase"

tandfonline.com/doi/abs/10.310…

#lcl6