Interplay between NAD+ and acetyl‑CoA metabolism in ischemia-induced mitochondrial pathophysiology

Nina Klimova, Aaron Long, Susana Scafidi, Tibor Kristian

Research output: Contribution to journalReview articlepeer-review

Abstract

Brain injury caused by ischemic insult due to significant reduction or interruption in cerebral blood flow leads to disruption of practically all cellular metabolic pathways. This triggers a complex stress response followed by overstimulation of downstream enzymatic pathways due to massive activation of post-translational modifications (PTM). Mitochondria are one of the most sensitive organelle to ischemic conditions. They become dysfunctional due to extensive fragmentation, inhibition of acetyl‑CoA production, and increased activity of NAD+ consuming enzymes. These pathologic conditions ultimately lead to inhibition of oxidative phosphorylation and mitochondrial ATP production. Both acetyl‑CoA and NAD+ are essential intermediates in cellular bioenergetics metabolism and also serve as substrates for post-translational modifications such as acetylation and ADP‑ribosylation. In this review we discuss ischemia/reperfusion-induced changes in NAD+ and acetyl‑CoA metabolism, how these affect relevant PTMs, and therapeutic approaches that restore the physiological levels of these metabolites leading to promising neuroprotection.

Original languageEnglish (US)
Pages (from-to)2060-2067
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1865
Issue number8
DOIs
StatePublished - Aug 1 2019

Keywords

  • Acetyl‑CoA
  • Brain
  • Ischemia
  • Mitochondria
  • NAD

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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