Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies

Abstract

Mitochondria are the powerhouses of the cell and are involved in essential functions of the cell, including ATP production, intracellular Ca²⁺ regulation, reactive oxygen species production & scavenging, regulation of apoptotic cell death and activation of the caspase family of proteases. Mitochondrial dysfunction and oxidative stress are largely involved in aging, cancer, age-related neurodegenerative and metabolic syndrome. In the last decade, tremendous progress has been made in understanding mitochondrial structure, function and their physiology in metabolic syndromes such as diabetes, obesity, stroke and hypertension, and heart disease. Further, progress has also been made in developing therapeutic strategies, including lifestyle interventions (healthy diet and regular exercise), pharmacological strategies and mitochondria-targeted approaches. These strategies were mainly focused to reduce mitochondrial dysfunction and oxidative stress and to maintain mitochondrial quality in metabolic syndromes. The purpose of our article is to highlight the recent progress on the mitochondrial role in metabolic syndromes and also summarize the progress of mitochondria-targeted molecules as therapeutic targets to treat metabolic syndromes. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

Keywords: Cardiovascular disease; Metabolic syndrome; Mitochondria; Mitochondria-targeted antioxidants; Obesity; Oxidative stress; Pre-diabetes; Reactive oxygen species; Type-2-diabetes.

Figure 1

Risk factors associated with metabolic syndrome.

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Generation of reactive oxygen species in mitochondrion

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Pathways involved in mitochondrial biogenesis

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(A). Mitochondrial fusion process (B). Mitochondrial fission process

Figure 4

(A). Mitochondrial fusion process (B). Mitochondrial fission process

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