Effects of carotenoids on mitochondrial dysfunction

Abstract

Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.

Keywords: astaxanthin; carotenoids; mitochondria; oxidative stress; reactive oxygen species.

Figure 1.. Chemical structures of common carotenes and xanthophylls.

Figure 2.. Overview of carotenoid metabolism with relevance to BCO1 and BCO2 enzymes.

Carotenoids, found in circulating lipoproteins enter cells through distinct mechanisms involving various receptors and transporters, such as scavenger receptor class B type I, low-density lipoprotein receptor, CD36 membrane transporters, and lipoprotein lipase. Once inside the cells, carotenoids bind to carotenoid-binding proteins and become integrated into cytoplasmic lipid droplets, as well as plasma and mitochondrial membranes. Provitamin A type carotenoids such as β-carotene are symmetrically cleaved by β-carotene oxygenase 1 (BCO1) to yield retinal directly. Mitochondrial BCO2, on the other hand, asymmetrically cleaves carotenoids. The resulting carotenoid cleavage products (apo carotenoids) can be converted into retinal by BCO1. Carotenoids and retinal are transported to the cell nucleus and exert their influence on gene expression (antioxidant genes such as Nrf2 and ERK, anti-apoptotic genes such as Bcl-2 and anti-inflammatory genes) by interacting with nuclear receptors and transcription factors.