Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation.
Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function.
Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting.
Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways.
Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors.
1Division of Extramural Research and Training, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA; 2Nicholas School of the Environment, Duke University, Durham, North Carolina, USA; 3Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; 4University of Pittsburgh Cancer Institute, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; 5Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA; 6Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 7Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, Massachusetts, USA; 8SUNY College of Nanoscale Science and Engineering, Albany, New York, USA; 9Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; 10Duke University Medical Center, Durham, North Carolina, USA; 11Department of Medicine, and 12Department of Bioengineering, University of California San Diego, La Jolla, California, USA; 13Laboratory of Molecular Carcinogenesis, and 14Laboratory of Molecular Genetics, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA; 15Biomolecular Screening Branch, Division of the National Toxicology Program, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
Recommended Citation:
Daniel T. Shaughnessy,1 Kimberly McAllister,1 Leroy Worth,et al. Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress[J]. Environmental Health Perspectives,2014-01-01,Volume 122(Issue 12):1271