Cellular and mitochondrial effects of alcohol consumption

Abstract

Alcohol dependence is correlated with a wide spectrum of medical, psychological, behavioral, and social problems. Acute alcohol abuse causes damage to and functional impairment of several organs affecting protein, carbohydrate, and fat metabolism. Mitochondria participate with the conversion of acetaldehyde into acetate and the generation of increased amounts of NADH. Prenatal exposure to ethanol during fetal development induces a wide spectrum of adverse effects in offspring, such as neurologic abnormalities and pre- and post-natal growth retardation. Antioxidant effects have been described due to that alcoholic beverages contain different compounds, such as polyphenols as well as resveratrol. This review analyzes diverse topics on the alcohol consumption effects in several human organs and demonstrates the direct participation of mitochondria as potential target of compounds that can be used to prevent therapies for alcohol abusers.

Keywords: alcohol consumption; antioxidants; mitochondria; oxidative stress.

Figure 1

Oxidative pathways of alcohol metabolism. The enzymes alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase all contribute to oxidative metabolism of alcohol. ADH, present in the cytosol, converts ethanol to acetaldehyde. This reaction involves an intermediate carrier of electrons, nicotinamide adenine dinucleotide (NAD⁺), which is reduced by two electrons to form NADH. Catalase, located in peroxisomes, requires hydrogen peroxide (H₂O₂) to oxidize alcohol. CYP2E1, present predominantly in the cell’s microsomes metabolize alcohol to acetaldehyde at elevated ethanol concentrations. Acetaldehyde is metabolized mainly by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria to form acetate and NADH (Adapted from [34]).

Figure 2

Ethanol effects on mitochondrial function. Alcohol is metabolized to acetaldehyde by the cytosolic enzyme alcohol dehydrogenase (ADH). Mitochondrial aldehyde dehydrogenase 2 (ALDH2) converts acetaldehyde to acetate. When this enzyme is malfunctioning, acetaldehyde increases and damages the electron transport complexes (CI-CIV) leading over production of reactive oxygen species (ROS), affecting electron transport chain (ETC) and oxidative phosphorylation disturbing ATP synthesis. Also, oxidative stress affects the permeability of the outer/inner mitochondrial membranes (OMM/IMM) promoting opening of the permeability transition pore (PTP) favoring the translocation of the pro-apoptotic factor bax, which forms a complex with voltage-dependent anion channel (VDAV). When the mitochondrial permeability transition is extensive, promotes the mitochondrial swelling and permits the cytochrome c release (Cyt c), caspase activation and DNA fragmentation, leading the programmed cell death or apoptosis. MM, mitochondrial matrix; ΔΨm, mitochondrial membrane potential. IMS, intramitochondrial space; Apaf-1, Apoptotic protease activating factor-1; ATP, adenosine triphosphate; ADP, adenosine diphosphate.