Degradation of phospholipids by oxidative stress—Exceptional significance of cardiolipin

Abstract

The aim of this study was to investigate the effect of oxidative stress on mitochondrial phospholipids. In this context, this study investigated (i) the content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and cardiolipin (CL), (ii) the correlation of CL degradation with mitochondrial function and (iii) the correlation of CL degradation and CL oxidation. Oxidative stress induced by iron/ascorbate caused a dramatic decrease of these phospholipids, in which CL was the most sensitive phospholipid. Even moderate oxidative stress by hypoxia/reoxygenation caused a decrease in CL that was parallelled by a decrease in active respiration of isolated rat heart mitochondria. The relation between oxidative stress, CL degradation and CL oxidation was studied by in vitro treatment of commercially available CL with superoxide anion radicals and H2O2. The degradation of CL was mediated by H2O2 and required the presence of cytochrome c. Other peroxidases such as horse radish peroxidase and glutathione peroxidase had no effect. Cytochrome c in the presence of H2O2 caused CL oxidation. The data demonstrate that oxidative stress may cause degradation of phospholipids by oxidation, in particular CL; resulting in mitochondrial dysfunction.

Multistep and multitask Bax activation

“…Indeed mitochondria are juxtaposed to endoplasmic reticulum (ER), especially close to areas rich in inositol-3-phosphate receptors (IP3r), (Rizzuto et al, 1998) and take up much of the IP3-induced Ca 2+ effluxes (Landolfi et al, 1998), when present in ER membranes (Zong et al, 2003), Bax increases the extent of such effluxes, promoting very high Ca 2+ levels in mitochondrial micro-domains (Wiswedel et al, 2010), compatible with a disturbance of cardiolipin anchorage.…”

“…In fact, Bcl-2 physically interacts with IP3r (Rong et al, 2009), reducing its activation in response to IP3 challenge (Chen et al, 2004); in the presence of Bax or Bak, this interaction is loosened, suggesting that in this instance Bax may interact with, and sequester, Bcl-2, thus interfering with its pro-survival effect at the ER level (Scorrano et al, 2003). Bax-mediated promotion of IP3-mediated efflux increases Ca 2+ concentration of vicinal mitochondria, favoring PTP and cardiolipin oxidation and promoting cytochrome c release (Wiswedel et al, 2010). Interestingly, the released cytochrome c may physically interact with IP3r, and this prevents closure of the IP3 channel after the initial Ca 2+ efflux, thus transforming a transient into a sustained efflux (Boehning et al, 2003).…”

The Effects of High Fat Diets With and Without N-Acetylcysteine Supplementation on the Lipin-1 Levels of Serum and Various Tissues in Rats

“…In addition, HFD increases oxidative stress and mitochondrial damage [32]. Oxidative stress may cause the degradation of phospholipids (in particular cardiolipin) by oxidation, resulting in mitochondrial dysfunction [33] which is a major contributor in heart failure [34]. The substrate of lipin-1, phosphatidate, is converted to various phospholipids including cardiolipin, a critical component of mitochondrial membranes [35].…”

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

“…(24) Cardiolipin peroxidation also leads to increased superoxide generation from the electron transport chain in the mitochondrion [59,62].…”

“…Because of the very rapid reaction of these two compounds to produce ONOO − , this partial uncoupling involving nearby NOS enzymes is expected to produce an increase in ONOO − production [8,10]. (23) Cardiolipin peroxidation leads to lowered activity of some of the enzymes in the electron transport chain, leading to further lowering of ATP synthesis [59][60][61][62].…”