Review Advance Publication
Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress
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Citation: Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol R, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1408418.
Received: 13 March 2014
Accepted: 14 August 2014
Advance Publication: 15 August 2014
PDF Version (1.8 MB)
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 (TCA) cycle, and mitochondria-nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation.
Objectives: This review investigates the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function.
Methods: NIEHS sponsored a workshop on Mitochondria, Energetics, Epigenetics, Environment and DNA Damage Response on March 25-26, 2013. Key points and ideas emerging from this meeting are summarized.
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 mitochondrial-cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors.
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