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The Mitochondrial-Derived Peptide (MOTS-c) Interacted with Nrf2 to Defend the Antioxidant System to Protect

Jingsong Xiao1, Qifu Zhang1, Yaohui Shan1

  • 1Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China.

Molecular Neurobiology
|June 28, 2023
PubMed

Insights

Mitochondria-derived peptide MOTS-c protects against rotenone-induced neurotoxicity by activating the Nrf2 antioxidant pathway. This peptide shields dopaminergic neurons from oxidative stress and cell damage in both cell cultures and animal models.

Area of Science:

  • Neuroscience
  • Mitochondrial Biology
  • Oxidative Stress Research

Background:

  • Mitochondria-derived peptide MOTS-c regulates energy metabolism.
  • The role of MOTS-c in neurodegeneration, particularly dopaminergic neurotoxicity, remains largely unexplored.
  • Rotenone is a common agent used to induce dopaminergic neurotoxicity in research models.

Purpose of the Study:

  • To investigate the protective effects of MOTS-c against rotenone-induced dopaminergic neurotoxicity.
  • To elucidate the underlying molecular mechanisms of MOTS-c action in this context.

Main Methods:

  • In vitro studies using PC12 cells exposed to rotenone.
  • In vivo studies using a rat model of rotenone-induced neurotoxicity.
  • Analysis of protein expression (TH, PSD95, SYP, Nrf2, HO-1, NQO1, Keap1) and cellular localization of MOTS-c.

Main Results:

  • Rotenone exposure altered MOTS-c expression and induced its translocation from mitochondria to the nucleus in PC12 cells.
  • Nuclear MOTS-c directly interacted with Nrf2, regulating antioxidant genes HO-1 and NQO1.
  • Exogenous MOTS-c pretreatment protected PC12 cells and rats against rotenone-induced mitochondrial dysfunction and oxidative stress.
  • MOTS-c pretreatment preserved dopaminergic neuron markers and modulated the Nrf2/HO-1/NQO1 pathway in vivo.

Conclusions:

  • MOTS-c exhibits neuroprotective properties against rotenone-induced dopaminergic neurotoxicity.
  • MOTS-c activates the Nrf2/HO-1/NQO1 signaling pathway, enhancing antioxidant defense.
  • MOTS-c represents a potential therapeutic target for neurodegenerative diseases involving oxidative stress.
Keywords:
Dopaminergic neuronMOTS-cMitochondrial dysfunctionNrf2Oxidative stressRotenone

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