title: Pheochromocytoma: Gasping for Air.
abstract: There has been increasing evidence that pseudohypoxia--a phenomenon that we refer to as "gasping for air"--along with mitochondrial enzyme dysregulation play a crucial role in tumorigenesis, particularly in several hereditary pheochromocytomas (PHEOs) and paragangliomas (PGLs). Alterations in key tricarboxylic acids (TCA) cycle enzymes (SDH, FH, MDH2) have been shown to induce pseudohypoxia via activation of the hypoxia-inducible transcription factor (HIF) signaling pathway that is involved in tumorigenesis, invasiveness, and metastatic spread, including an association with resistance to various cancer therapies and worse prognosis. This review outlines the ongoing story of the pathogenesis of hereditary PHEOs/PGLs, showing the unique and most updated evidence of TCA cycle dysregulation that is tightly linked to hypoxia signaling.
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver NICHD, National Institutes of Health, Building 10, CRC, 1-East, Room 1E-3140, 10 Center Drive, MSC-1109, Bethesda, MD, 20892-1109, USA.|1st Department of Internal Medicine, Medical Faculty, P. J. Šafárik University in Košice, Trieda SNP 1, 04011, Košice, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jochmanová
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver NICHD, National Institutes of Health, Building 10, CRC, 1-East, Room 1E-3140, 10 Center Drive, MSC-1109, Bethesda, MD, 20892-1109, USA. karel@mail.nih.gov.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002952:Citric Acid Cycle; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010100:Oxygen