Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis

Abstract

The temporal sequence combined with the recently demonstrated role of CL hydroperoxides (CL-OOH) in in vitro models of apoptosis suggest that CL-OOH may be both a key in vivo trigger of apoptotic cell death and a therapeutic target in experimental traumatic brain injury.

Deciphering of Mitochondrial Cardiolipin Oxidative Signaling in Cerebral Ischemia-Reperfusion

“…Molecular speciation of phospholipid classes corresponded to the previously published data. 10 While CA did not cause large changes in either molecular speciation or levels of individual phospholipids, detailed analysis of lysophospholipis ( Figure 2B) revealed accumulation of monolyso-CL ( Figure 2C). Other classes of lysophospholipids did not undergo statistically significant increases ( Figure 2C).…”

“…The selectivity of CA-induced CL modification is surprising given that CL constitutes only a small fraction (~2 mol%) of all brain phospholipids. 10 Quantitative correspondence of lyso-CLs and FFAox suggests that oxidized CLs were the major substrates of PLA 2 -catalyzed hydrolysis and release of these products. This is further supported by data showing that only small amounts of FFAox were detected when lipid extracts were hydrolyzed by a mixture of exogenously added PLA 1 +PLA 2 ( Figure 9).…”

“…9 Delivery of oxygen to dysfunctional mitochondria may be associated with generation of ROS and peroxidation of polyunsaturated phospholipids, particularly cardiolipin (CL), as has been documented for traumatic brain injury. 10 Recently, we discovered that peroxidized CL can be hydrolyzed by mitochondrial Ca 2+ -independent iPLA 2 γ and release oxygenated PUFA. 11 Thus, two different pathwaysone initiated by Ca 2+ -dependent PLA 2 with subsequent oxygenation of PUFA by COX and LOX, or the other involving Ca 2 + -independent CL oxidation by cytochrome c with subsequent hydrolysis by iPLA 2 γ-may result in the production of a variety of lipid mediators after CA ( Figure 1).…”

Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression

“…O xidative stress causes mitochondrial dysfunction, which has been implicated in aging and age-related diseases (1)(2)(3). Although the underlying causes remain elusive, disrupted mitochondrial dynamics by reactive oxygen species (ROS) has been implicated in mitochondrial pathogenesis in these conditions (4)(5)(6). The onset of diabetes is associated with mitochondrial fragmentation in islet β-cells, endothelial cells, and neurons attributable to a fusion defect (4)(5)(6).…”

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

“…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].…”