The peroxisomal enzyme, FAR1, is induced during ER stress in an ATF6- dependent manner in cardiac myocytes

Kayleigh G. Marsh, Adrian Arrieta, Donna J. Thuerauf, Erik A. Blackwood, Lauren MacDonnell, Christopher C. Glembotski

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Although peroxisomes have been extensively studied in other cell types, their presence and function have gone virtually unexamined in cardiac myocytes. Here, in neonatal rat ventricular myocytes (NRVM) we showed that several known peroxisomal proteins co-localize to punctate structures with a morphology typical of peroxisomes. Surprisingly, we found that the peroxisomal protein, fatty acyl- CoA reductase 1 (FAR1), was upregulated by pharmacological and pathophysiological ER stress induced by tunicamycin (TM) and simulated ischemia-reperfusion (sI/R), respectively. Moreover, FAR1 induction in NRVM was mediated by the ER stress sensor, activating transcription factor 6 (ATF6). Functionally, FAR1 knockdown reduced myocyte death during oxidative stress induced by either sI/R or hydrogen peroxide (H2O2). Thus, Far1 is an ER stress-inducible gene, which encodes a protein that localizes to peroxisomes of cardiac myocytes, where it reduces myocyte viability during oxidative stress. Since FAR1 is critical for plasmalogen synthesis, these results imply that plasmalogens may exert maladaptive effects on the viability of myocytes exposed to oxidative stress.

Original languageEnglish (US)
Pages (from-to)H1813-H1821
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume320
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • ATF6
  • Cardiomyocyte
  • FAR1
  • Ischemia-reperfusion
  • Peroxisome

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'The peroxisomal enzyme, FAR1, is induced during ER stress in an ATF6- dependent manner in cardiac myocytes'. Together they form a unique fingerprint.

Cite this