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Updated: Oct 21, 2025

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria
06:55

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

Published on: August 4, 2022

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HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons

Cécile A Ferré1, Anne Thouard1, Alexandre Bétourné1

  • 1Toulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPS, Toulouse, France.

Scientific Reports
|September 7, 2021
PubMed

Insights

Mortalin, a key protein for mitochondrial health, is crucial for neuronal survival. Its reduced levels trigger axonal damage, while higher levels protect neurons, highlighting its role in neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Mortalin is a mitochondrial chaperone protein regulating protein import and sensing neuronal stress.
  • Down-regulation of Mortalin is observed in neurodegenerative diseases, correlating with neuronal fate.
  • The precise mechanisms linking Mortalin levels, mitochondrial function, and neurodegeneration remain unclear.

Purpose of the Study:

  • To investigate the role of Mortalin in neuronal stress and neurodegeneration.
  • To elucidate the impact of Mortalin levels on mitochondrial function, morphology, and axonal integrity.
  • To explore Mortalin's modulation of mitochondrial dynamics in the context of neurodegenerative diseases.

Main Methods:

  • Primary neuronal cultures were established using lentiviral vectors for Mortalin over-expression and under-expression.
  • Oriented neuronal cultures in microfluidic devices were used to analyze early neurodegenerative events in axons.
  • Mitochondrial morphology, axonal damage, and DRP1 phosphorylation were assessed in response to altered Mortalin levels and rotenone exposure.

Main Results:

  • Mortalin down-regulation led to mitochondrial fragmentation and axonal damage.
  • Mortalin over-expression protected against rotenone-induced axonal degeneration.
  • Mortalin levels were shown to modulate mitochondrial morphology via DRP1 phosphorylation.

Conclusions:

  • Mortalin plays a critical role in maintaining axonal integrity and neuronal survival.
  • Altered Mortalin expression significantly impacts mitochondrial dynamics and neuronal fate.
  • Targeting Mortalin or modulating mitochondrial dynamics may offer therapeutic strategies for neurodegenerative diseases.

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