1. Academic Validation
  2. Effects of itaconic acid on neuronal viability and brain mitochondrial functions

Effects of itaconic acid on neuronal viability and brain mitochondrial functions

  • J Bioenerg Biomembr. 2021 Oct;53(5):499-511. doi: 10.1007/s10863-021-09911-6.
Danielius Umbrasas 1 2 Paulius Čižas 3 Odeta Arandarčikaitė 3 Tadas Vanagas 3 Vilmantė Borutaitė 3
Affiliations

Affiliations

  • 1 Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania. danielius.umbrasas@lsmuni.lt.
  • 2 Faculty of Medicine, Department of Biochemistry, Lithuanian University of Health Sciences, Kaunas, Lithuania. danielius.umbrasas@lsmuni.lt.
  • 3 Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Abstract

Recent studies have identified that under stimulation by Bacterial lipopolysaccharide mammalian macrophages produce itaconic acid. Yet, it is unknown whether itaconate has any effect on viability of brain cells. Here we used extracellularly added itaconate to investigate its effects on viability of cerebellar granule cells (CGC) in cultures and respiratory functions of these cells and isolated brain mitochondria. We found that 3-5 mM itaconate had no effect on the viability of neurons, but 10 mM itaconate was toxic and induced neuronal Apoptosis. Removal of itaconate after 24 h incubation resulted in further decrease in viability and number of neurons. Respiration of intact neurons was not affected by itaconate, but permeabilized cells as well as isolated brain mitochondria demonstrated decreased rates of respiration in the presence of itaconate. Using isolated adult rat brain mitochondria we found that itaconate decreased mitochondrial phosphorylating respiration, mitochondrial calcium retention capacity, production of Reactive Oxygen Species with Complex I and Complex II substrates as well as inhibition of Complex I, Complex IV and ATP Synthase. In conclusion, the results suggest that itaconic acid at millimolar concentrations affects mitochondrial functions and viability of neurons.

Keywords

Brain; Itaconic acid; Mitochondria; Neuron; Respiration.

Figures
Products