Neurodegeneration with brain iron accumulation: Insights into the mitochondria dysregulation

Biomed Pharmacother. 2019 Oct:118:109068. doi: 10.1016/j.biopha.2019.109068. Epub 2019 Aug 9.


NBIA (Neurodegeneration with brain iron accumulation) is a group of inherited neurologic disorders characterized by marked genetic heterogeneity, in which iron atypical accumulates in basal ganglia resulting in brain magnetic resonance imaging changes, histopathological abnormalities, and neuropsychiatric clinical symptoms. With the rapid development of high-throughput sequencing technologies, ten candidate genes have been identified, including PANK2, PLA2G6, C19orf12, WDR45, FA2H, ATP13A2, FTL, CP, C2orf37, and COASY. They are involved in seemingly unrelated cellular pathways, such as iron homeostasis (FTL, CP), lipid metabolism (PLA2G6, C19orf12, FA2H), Coenzyme A synthesis (PANK2, COASY), and autophagy (WDR45, ATP13A2). In particular, PANK2, COASY, PLA2G6, and C19orf12 are located on mitochondria, which associate with certain subtypes of NBIA showing mitochondria dysregulation. However, the relationships among those four genes are still unclear. Therefore, this review is specifically focused on dysregulation of mitochondria in NBIA and afore-mentioned four genes, with summaries of both pathological and clinical findings.

Keywords: C19orf12; COASY; Mitochondria; Neurodegeneration with brain iron accumulation; PANK2; PLA2G6.

Publication types

  • Review

MeSH terms

  • Group VI Phospholipases A2 / genetics*
  • Humans
  • Iron Metabolism Disorders / genetics*
  • Iron Metabolism Disorders / metabolism
  • Iron Metabolism Disorders / pathology
  • Lipid Metabolism / genetics
  • Membrane Potential, Mitochondrial / genetics
  • Mitochondria / pathology*
  • Mitochondrial Proteins / genetics*
  • Neuroaxonal Dystrophies / genetics*
  • Neuroaxonal Dystrophies / metabolism
  • Neuroaxonal Dystrophies / pathology
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Transferases / genetics*


  • C19orf12 protein, human
  • Mitochondrial Proteins
  • Transferases
  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase
  • COASY protein, human
  • Group VI Phospholipases A2
  • PLA2G6 protein, human

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)