View source for Formation of 4-hydroxynonenal from cardiolipin oxidation: intramolecular peroxyl radical addition and decomposition (2011)

== Explanation ==
This paper describes how [[4-hydroxy-2-nonenal (4-HNE)]] can form inside our cells. The membranes of our [[mitochondria]] are made of [[cardiolipin]], which contains [[polyunsaturated fatty acids (PUFAs)]]. The [[oxidation]] of these fats leads to the formation of 4-HNE. 

== Highlights ==
TBA

== Related Studies ==
TBA

== Official Abstract ==
<blockquote>We report herein that oxidation of a mitochondria-specific phospholipid tetralinoleoyl cardiolipin (L4CL) by cytochrome c and H2O2 leads to the formation of 4-hydroxy-2-nonenal (4-HNE) via a novel chemical mechanism which involves cross-chain peroxyl radical addition and decomposition. As one of the most bioactive lipid electrophiles, 4-HNE possesses diverse biological activities ranging from modulation of multiple signal transduction pathways to the induction of intrinsic apoptosis. However, where and how 4-HNE is formed in vivo is much less understood. Recently a novel chemical mechanism has been proposed that involves inter- molecular dimerization of fatty acids by peroxyl bond formation; but the biological relevance of this mechanism is unknown because a majority of the fatty acids are esterified in phospholipids in the cellular membrane. We hypothesize that oxidation of cardiolipins, especially L4CL, may lead to the formation of 4-HNE via this novel mechanism. We employed L4CL and di-linoleoyl- phosphatidylcholine (DLPC) as model compounds to test this hypothesis. Indeed, in experiments designed to assess the intramolecular mechanism, more 4-HNE is formed from L4CL and DLPC oxidation than 1-palmitoyl-2-linoleoyl-phosphatydylcholine (PLPC). The key products and intermediates that are consistent with this proposed mechanism of 4-HNE formation have been identified using liquid chromatography – mass spectrometry (LC-MS) methods. Identical products from cardiolipin oxidation were identified in vivo in rat liver tissue after carbon tetrachloride treatment. Our studies provide the first evidence in vitro and in vivo for the formation 4-HNE from cardiolipin oxidation via cross-chain peroxyl radical addition and decomposition, which may have implications in apoptosis and other biological activities of 4-HNE.</blockquote>

== Publication Details ==

=== Authors ===
[[Wei Liu]], [[Ned A. Porter]], [[Claus Schneider]], [[Alan R. Brash]], and [[Huiyong Yin]]

=== Journal ===
[[Free Radical Biology and Medicine]]

=== PubMed ===
https://pubmed.ncbi.nlm.nih.gov/21047551/

=== Full Text ===
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014443/

=== Citation ===
Liu W, Porter NA, Schneider C, Brash AR, Yin H. Formation of 4-hydroxynonenal from cardiolipin oxidation: Intramolecular peroxyl radical addition and decomposition. Free Radic Biol Med. 2011 Jan 1;50(1):166-78. doi: 10.1016/j.freeradbiomed.2010.10.709. Epub 2010 Nov 1. PMID: 21047551; PMCID: PMC3014443.
[[Category:Research Papers]]
[[Category:Apoptosis]]
[[Category:Cardiolipin]]
[[Category:Lipid peroxidation]]
[[Category:4-hydroxy-2-nonenal (4-HNE)]]
[[Category:Free radicals]]
[[Category:Cytochrome c]]
[[Category:Mitochondria]]