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Mitochondria are a substrate of cellular memory.

Amin Cheikhi1, Callen Wallace2, Claudette St Croix3

  • 1Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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Summary

Mitochondria store cellular stress memory through enduring physicochemical changes called mitoengrams. Erasing these mitoengrams can reset epigenetic marks and restore normal cell identity, revealing mitochondria

Keywords:
ArsenicCellular memoryEpigeneticsMitochondriaXJB-5-131

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Area of Science:

  • Cellular Biology
  • Epigenetics
  • Mitochondrial Biology

Background:

  • Cellular memory is crucial for identity, adapting to genetic and environmental factors.
  • Epigenetic modifications play a key role in maintaining cellular memory across generations.
  • Mitochondria are increasingly recognized for their roles beyond energy production, including signaling and memory.

Purpose of the Study:

  • To investigate the role of mitochondria in the persistence of cellular memory.
  • To identify the mechanism by which stress-induced cellular behaviors are transmitted across cell generations.
  • To explore the potential for targeting mitochondria to modulate cellular memory.

Main Methods:

  • Utilized C2C12 myogenic stem-like cells exposed to transient, low-level arsenite stress.
  • Investigated the phenomenon of 'mitoengrams'—enduring physicochemical changes in mitochondrial networks.
  • Employed mitochondria-targeted electron scavengers to attempt erasure of mitoengrams.

Main Results:

  • Demonstrated that transient stress induces lasting changes in mitochondrial networks (mitoengrams).
  • Showed that stress memory is stored in a self-renewing cell subpopulation via mitochondria.
  • Confirmed that erasing mitoengrams resets epigenetic marks and alters progeny cell identity.

Conclusions:

  • Mitoengrams represent a mechanism for transgenerational epigenetic inheritance of cellular behavior.
  • Mitochondrial physicochemical changes are key to storing and transmitting cellular stress memory.
  • Targeting mitochondria offers a potential strategy to control the persistence and transience of cellular memory.