title: Mitochondria, energetics, epigenetics, and cellular responses to stress.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division 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.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Shaughnessy
authors.forename: Kimberly
authors.initials: K
authors.lastname: McAllister
authors.forename: Leroy
authors.initials: L
authors.lastname: Worth
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Haugen
authors.forename: Joel N
authors.initials: JN
authors.lastname: Meyer
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann
authors.forename: Bennett
authors.initials: B
authors.lastname: Van Houten
authors.forename: Raul
authors.initials: R
authors.lastname: Mostoslavsky
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Bultman
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Begley
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sobol
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hirschey
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
authors.forename: Janine H
authors.initials: JH
authors.lastname: Santos
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tice
authors.forename: David M
authors.initials: DM
authors.lastname: Balshaw
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Tyson
mesh_terms: D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D054629:Genome, Mitochondrial; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D004785:Environmental Pollutants