ALD is one of the most common causes of chronic liver disease in the United States, and many other countries. ALD represents a wide spectrum of liver damage ranging from alcoholic steatosis, to alcoholic steatohepatitis (ASH), to cirrhosis. ASH represents a stage within the spectrum of ALD that is characterized by the accumulation of lipid stores in the liver (steatosis) along with inflammation and different degrees of scarring or fibrosis (8). ASH is potentially serious condition, as patients with ASH are at particular risk for disease progression to cirrhosis and its complications including portal hypertension, liver failure and hepatocellular carcinoma (4, 9). Chronic ethanol consumption alters liver mitochondria structure as well as function (2-5), and recent work suggests that this chronic ethanol-related disturbance in mitochondria health might also be responsible for an increased production of ROS, a central abnormality responsible for liver injury and disease progression in ALD (6-12). The central question extant is what events link excess alcohol consumption to mitochondrial dysfunction. Small increases in mitochondrial ROS production may lead to subsequent severe derangement and massive ROS production, membrane potential collapse, swelling and cytochrome c release (13). These events proceed, and are responsible for, apoptotic cell death. The peroxide function of phospholipid (hydro)peroxides are chemically reactive and can disintegrate to form a variety of fragmented phospholipids with varied sn-2 residues. Phospholipid hydroperoxides also are the source of free fatty acid hydroperoxides, and so are early markers of oxidative stress. Some of these phospholipid oxidation products potently disrupt mitochondrial structure with cytochrome c release in in vitro assays. These are more than markers of oxidation because we find (1) that fragmented phospholipids readily enter cells, damage mitochondria in situ, and initiate the intrinsic apoptotic cascade.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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Zhou, Hao; Yu, Minjia; Zhao, Junjie et al. (2016) IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. Hepatology 64:1978-1993
Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina et al. (2016) Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice. J Nutr Biochem 27:16-26
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Golub, Haleigh M; Zhou, Qi-Gang; Zucker, Hannah et al. (2015) Chronic Alcohol Exposure is Associated with Decreased Neurogenesis, Aberrant Integration of Newborn Neurons, and Cognitive Dysfunction in Female Mice. Alcohol Clin Exp Res 39:1967-77
Latchoumycandane, Calivarathan; Nagy, Laura E; McIntyre, Thomas M (2015) Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption. Free Radic Biol Med 86:179-90

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