[Frontiers in Bioscience 12, 1238-1246, January 1, 2007]

Impairment of mitochondrial function by particulate matter (PM) and their toxic components: implications for PM-induced cardiovascular and lung disease

Tian Xia, Michael Kovochich, and Andre E. Nel

Division of Clinical Immunology and Allergy, Department of Medicine; Southern California Particle Center and Supersite, University of California, Los Angeles, CA


1. Abstract
2. Introduction
3. Biological pathways of PM-induced ROS generation
4. PM perturbation of mitochondrial function
4.1. Mechanism 1: Effects on the mitochondrial electron transfer chain
4.2. Mechanism 2: Effects on permeability transition pore opening
4.3. Mechanism 3: Indirect PM effects on mitochondrial function
4.4. Mechanism 4: Direct physical targeting of mitochondria with structural damage.
5. Disease and secondary consequences of PM-induced mitochondrial damage
5.1. Airway disease
5.2. Cardiovacular disease
6. Summary
7. Acknowledgements
8. References


Increasing evidence suggests that reactive oxygen species (ROS) and oxidative stress are involved in PM-mediated lung and cardiovascular injury. The physical characteristics and the chemical composition of particulate matter (PM) play a key role in ROS generation in vitro and in vivo. The mitochondria are major subcellular targets for PM as well as a source of ROS production. ROS production is due to interference in mitochondrial electron transfer and PT pore opening by pro-oxidative PM components. Another possible mechanism is direct physical targeting by ambient ultrafine particles that lodge in and destroy mitochondrial structure. An understanding of the mitochondrial effects of PM is key in understanding the mechanisms of PM-induced adverse health effects.