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 journalArticlepeer-review

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 2019

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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