title: SOD2 and the Mitochondrial UPR: Partners Regulating Cellular Phenotypic Transitions.
abstract: ATP and reactive oxygen species (ROS) are signaling molecules that control cellular function and phenotype. Mitochondria produce both ATP and ROS. Since the electrons needed to generate either ATP or ROS originate from NADH/FADH2, the mechanism through which electrons flow towards oxygen determines yields and whether ATP or ROS prevails. Alterations in the electron flow impact cells dramatically, such as by supporting specialization (which requires high ATP) or imposing dedifferentiation. High ROS, facilitated by enzymes such as superoxide dismutase 2 (SOD2) that enhance mitochondrial hydrogen peroxide (mtH2O2), are normally linked to dedifferentiation of somatic cells. Here we propose that combined high mtH2O2 and mitochondrial unfolded protein response (UPR(mt)) activation are essential for somatic dedifferentiation programs and the acquisition of stem-like properties in reparative processes and disease.
authors.affiliation: Department of Medicine, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pharmacology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pathology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Chenxia
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Medicine, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pharmacology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pathology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hart
authors.affiliation: Department of Medicine (Hematology and Medical Oncology), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Germain
authors.affiliation: Department of Medicine, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pharmacology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pathology, College of Medicine of the University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: mbonini@uic.edu.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Bonini
mesh_terms: D000818:Animals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D056811:Unfolded Protein Response; D000099156:Superoxide Dismutase 2
chemical_list: D006861:Hydrogen Peroxide; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2