title: Mitochondrial thiols in the regulation of cell death pathways.
abstract: CONCLUSIONS
  Regulation of mitochondrial H(2)O(2) homeostasis and its involvement in the regulation of redox-sensitive signaling and transcriptional pathways is the consequence of the concerted activities of the mitochondrial energy- and redox systems.
  
  
  BACKGROUND
  The energy component of this mitochondrial energy-redox axis entails the formation of reducing equivalents and their flow through the respiratory chain with the consequent electron leak to generate [Formula: see text] and H(2)O(2). The mitochondrial redox component entails the thiol-based antioxidant system, largely accounted for by glutathione- and thioredoxin-based systems that support the activities of glutathione peroxidases, peroxiredoxins, and methionine sulfoxide reductase. The ultimate reductant for these systems is NADPH: mitochondrial sources of NADPH are the nicotinamide nucleotide transhydrogenase, isocitrate dehydrogenase-2, and malic enzyme. NADPH also supports the glutaredoxin activity that regulates the extent of S-glutathionylation of mitochondrial proteins in response to altered redox status.
  
  
  RESULTS
  The integrated network of these mitochondrial thiols constitute a regulatory device involved in the maintenance of steady-state levels of H(2)O(2), mitochondrial and cellular redox and metabolic homeostasis, as well as the modulation of cytosolic redox-sensitive signaling; disturbances of this regulatory device affects transcription, growth, and ultimately influences cell survival/death.
  
  
  CONCLUSIONS
  The modulation of key mitochondrial thiol proteins, which participate in redox signaling, maintenance of the bioenergetic machinery, oxidative stress responses, and cell death programming, provides a pivotal direction in developing new therapies towards the prevention and treatment of several diseases.
authors.affiliation: Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Harsh
authors.initials: H
authors.lastname: Sancheti
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D054464:Peroxiredoxins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D013438:Sulfhydryl Compounds; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase