2. Academic Validation
  3. Mitochondrial transplantation rescues neuronal cells from ferroptosis

Mitochondrial transplantation rescues neuronal cells from ferroptosis

  • Free Radic Biol Med. 2023 Nov 1:208:62-72. doi: 10.1016/j.freeradbiomed.2023.07.034.
Tingting Chen 1,  Nad'a Majerníková 2,  Alejandro Marmolejo-Garza 3,  Marina Trombetta-Lima 3,  Angélica María Sabogal-Guáqueta 4,  Yuequ Zhang 4,  Ruth Ten Kate 4,  Minte Zuidema 4,  Patty P M F A Mulder 5,  Wilfred den Dunnen 6,  Reinoud Gosens 4,  Elisabeth Verpoorte 5,  Carsten Culmsee 7,  Ulrich L M Eisel 8,  Amalia M Dolga 9
Affiliations

Affiliations

  • 1 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
  • 2 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
  • 3 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 4 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.
  • 5 Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.
  • 6 Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
  • 7 Institute of Pharmacology and Clinical Pharmacy, Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
  • 8 Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
  • 9 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands. Electronic address: a.m.dolga@rug.nl.
PMID: 37536459 DOI: 10.1016/j.freeradbiomed.2023.07.034
Abstract

Ferroptosis is a type of oxidative cell death that can occur in neurodegenerative diseases and involves damage to mitochondria. Previous studies demonstrated that preventing mitochondrial dysfunction can rescue cells from ferroptotic cell death. However, the complexity of mitochondrial dysfunction and the timing of therapeutic interventions make it difficult to develop an effective treatment strategy against Ferroptosis in neurodegeneration conditions. In this study, we explored the use of mitochondrial transplantation as a novel therapeutic approach for preventing ferroptotic neuronal cell death. Our data showed that isolated exogenous mitochondria were incorporated into both healthy and ferroptotic immortalized hippocampal HT-22 cells and primary cortical neurons (PCN). The mitochondrial incorporation was accompanied by increased metabolic activity and cell survival through attenuating lipid peroxidation and mitochondrial superoxide production. Further, the function of mitochondrial complexes I, III and V activities contributed to the neuroprotective activity of exogenous mitochondria. Similarly, we have also showed the internalization of exogenous mitochondria in mouse PCN; these internalized mitochondria were found to effectively preserve the neuronal networks when challenged with ferroptotic stimuli. The administration of exogenous mitochondria into the axonal compartment of a two-compartment microfluidic device induced mitochondrial transportation to the cell body, which prevented fragmentation of the neuronal network in ferroptotic PCN. These findings suggest that mitochondria transplantation may be a promising therapeutic approach for protecting neuronal cells from ferroptotic cell death.

Keywords

Ferroptosis; HT-22 cells; Mitochondrial transplantation; Oxidative stress; Primary cortical neurons.

Figures
Products