Mitochondria are a substrate of cellular memory

Amin Cheikhi, Callen Wallace, Claudette St Croix, Charles Cohen, Wan-Yee Tang, Peter Wipf, Panagiotis V. Benos, Fabrisia Ambrosio, Aaron Barchowsky

Research output: Contribution to journalArticle

Abstract

Cellular memory underlies cellular identity, and thus constitutes a unifying mechanism of genetic disposition, environmental influences, and cellular adaptation. Here, we demonstrate that enduring physicochemical changes of mitochondrial networks invoked by transient stress, a phenomenon we term ‘mitoengrams’, underlie the transgenerational persistence of epigenetically scripted cellular behavior. Using C2C12 myogenic stem-like cells, we show that stress memory elicited by transient, low-level arsenite exposure is stored within a self-renewing subpopulation of progeny cells in a mitochondrial-dependent fashion. Importantly, we demonstrate that erasure of mitoengrams by administration of mitochondria-targeted electron scavenger was sufficient to reset key epigenetic marks of cellular memory and redirect the identity of the mitoengram-harboring progeny cells to a non-stress-like state. Together, our findings indicate that mnemonic information emanating from mitochondria support the balance between the persistence and transience of cellular memory.

Original languageEnglish (US)
Pages (from-to)528-541
Number of pages14
JournalFree Radical Biology and Medicine
Volume130
DOIs
StatePublished - Jan 1 2019

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Mitochondria
Data storage equipment
Substrates
Epigenomics
Stem Cells
Electrons

Keywords

  • Arsenic
  • Cellular memory
  • Epigenetics
  • Mitochondria
  • XJB-5-131

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Cheikhi, A., Wallace, C., St Croix, C., Cohen, C., Tang, W-Y., Wipf, P., ... Barchowsky, A. (2019). Mitochondria are a substrate of cellular memory. Free Radical Biology and Medicine, 130, 528-541. https://doi.org/10.1016/j.freeradbiomed.2018.11.028

Mitochondria are a substrate of cellular memory. / Cheikhi, Amin; Wallace, Callen; St Croix, Claudette; Cohen, Charles; Tang, Wan-Yee; Wipf, Peter; Benos, Panagiotis V.; Ambrosio, Fabrisia; Barchowsky, Aaron.

In: Free Radical Biology and Medicine, Vol. 130, 01.01.2019, p. 528-541.

Research output: Contribution to journalArticle

Cheikhi, A, Wallace, C, St Croix, C, Cohen, C, Tang, W-Y, Wipf, P, Benos, PV, Ambrosio, F & Barchowsky, A 2019, 'Mitochondria are a substrate of cellular memory', Free Radical Biology and Medicine, vol. 130, pp. 528-541. https://doi.org/10.1016/j.freeradbiomed.2018.11.028
Cheikhi, Amin ; Wallace, Callen ; St Croix, Claudette ; Cohen, Charles ; Tang, Wan-Yee ; Wipf, Peter ; Benos, Panagiotis V. ; Ambrosio, Fabrisia ; Barchowsky, Aaron. / Mitochondria are a substrate of cellular memory. In: Free Radical Biology and Medicine. 2019 ; Vol. 130. pp. 528-541.
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