High-resolution respirometry reveals mpp+ mitochondrial toxicity mechanism in a cellular model of parkinson’s disease

Pierpaolo Risiglione, Loredana Leggio, Salvatore A.M. Cubisino, Simona Reina, Greta Paternò, Bianca Marchetti, Andrea Magrì, Nunzio Iraci, Angela Messina

Research output: Contribution to journalArticlepeer-review

Abstract

MPP+ is the active metabolite of MPTP, a molecule structurally similar to the herbicide Paraquat, known to injure the dopaminergic neurons of the nigrostriatal system in Parkinson’s disease models. Within the cells, MPP+ accumulates in mitochondria where it inhibits complex I of the electron transport chain, resulting in ATP depletion and neuronal impairment/death. So far, MPP+ is recognized as a valuable tool to mimic dopaminergic degeneration in various cell lines. However, despite a large number of studies, a detailed characterization of mitochondrial respiration in neuronal cells upon MPP+ treatment is still missing. By using high-resolution respirometry, we deeply investigated oxygen consumption related to each respiratory state in differentiated neuroblastoma cells exposed to the neurotoxin. Our results indicated the presence of extended mitochondrial damage at the inner membrane level, supported by increased LEAK respiration, and a drastic drop in oxygen flow devoted to ADP phosphorylation in respirometry measurements. Furthermore, prior to complex I inhibition, an enhancement of complex II activity was observed, suggesting the occurrence of some compensatory effect. Overall our findings provide a mechanistic insight on the mitochondrial toxicity mediated by MPP+, relevant for the standardization of studies that employ this neurotoxin as a disease model.

Original languageEnglish
Article number7809
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number21
DOIs
Publication statusPublished - Nov 1 2020

Keywords

  • High-resolution respirometry
  • Mitochondria
  • MPP
  • Parkinson’s disease
  • SH-SY5Y cells

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'High-resolution respirometry reveals mpp<sup>+</sup> mitochondrial toxicity mechanism in a cellular model of parkinson’s disease'. Together they form a unique fingerprint.

Cite this