Elevating bioavailable iron levels in mitochondria suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila melanogaster

Biochem Biophys Res Commun. 2020 Nov 5;532(2):285-291. doi: 10.1016/j.bbrc.2020.08.002. Epub 2020 Aug 29.

Abstract

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron deposit was found in the SNpc of PD patients and animal models, however, the mechanisms involved in disturbed iron metabolism remain unknown. Identifying the relationship between iron metabolism and PD is important for finding new therapeutic strategies. In this study, we found that transgenic overexpression (OE) of Drosophila mitoferrin (dmfrn) or knockdown of Fer3HCH significantly mitigated the reduced mitochondrial aconitase activity, abnormal wing posture, flight deficits and mitochondrial morphology defects associated with PINK1 loss-of-function (LOF). Further work demonstrated that dmfrn OE or Fer3HCH knockdown significantly rescued the impaired mitochondrial respiration in PINK1 LOF flies, indicating that dmfrn or Fer3HCH may rescue PINK1 LOF phenotypes through elevating mitochondrial bioavailable iron levels to promote mitochondrial respiration.

Keywords: Drosophila; Iron; Mitochondria; PINK1; Parkin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / metabolism
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biological Availability
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Gene Expression
  • Iron / metabolism*
  • Loss of Function Mutation
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Nerve Tissue Proteins / genetics
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Rotenone / toxicity
  • Wings, Animal / physiopathology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Fer3 protein, Drosophila
  • Mfrn protein, Drosophila
  • Nerve Tissue Proteins
  • Rotenone
  • Iron
  • PINK1 protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • Aconitate Hydratase