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Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial

Jackelyn M Kembro1, Sonia Cortassa2, Miguel A Aon2

  • 1Facultad de Ciencias Exactas, Físicas y Naturales, Instituto de Investigaciones Biológicas y Tecnológicas (Consejo Nacional de Investigaciones Científicas y Técnicas-UNC) and Instituto de Ciencia y Tecnología de los Alimentos, Universidad Nacional de Córdoba Córdoba, Argentina.

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Summary

Mitochondria act as biological timekeepers, exhibiting complex oscillations under oxidative stress. These dynamics, influenced by superoxide dismutase (SOD) levels, may serve as a signaling mechanism during cellular stress.

Keywords:
Hopf bifurcationsROS signalingcomplex oscillationsmitochondrial energetic/redoxphysiological and pathophysiological behaviorredox environment

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Area of Science:

  • Mitochondrial physiology
  • Cellular redox biology
  • Computational modeling

Background:

  • Oscillatory behavior is a conserved trait for timekeeping in biological systems.
  • Mitochondria regulate energy production and reactive oxygen species (ROS) for signaling.
  • Understanding mitochondrial dynamics is crucial for cellular health.

Purpose of the Study:

  • To explore timekeeping functions in mitochondrial dynamics using a computational model.
  • To investigate the relationship between mitochondrial energetic-redox balance and oscillatory behavior.
  • To determine the role of superoxide dismutase (SOD) in regulating these dynamics.

Main Methods:

  • Utilized the validated two-compartment mitochondrial energetic-redox (ME-R) computational model.
  • Incorporated key redox couples, scavenging systems, and ROS transport.
  • Performed power spectral and stability analyses to characterize model dynamics.

Main Results:

  • The ME-R model exhibited complex oscillatory dynamics with multiple frequencies.
  • Oscillatory behavior was dependent on Mn and Cu, Zn SOD concentrations and ROS production.
  • Complex oscillations occurred at the boundary of normal and pathological mitochondrial function, associated with oxidative stress.

Conclusions:

  • Complex mitochondrial oscillations may function as a frequency- and amplitude-modulated hydrogen peroxide (H2O2) signaling mechanism under oxidative stress.
  • Modulation of SOD provides an adaptive mechanism for cells to balance stability and flexibility under redox/energetic stress.
  • Mitochondrial dynamics play a critical role in cellular timekeeping and stress response.