Propionate hampers differentiation and modifies histone propionylation and acetylation in skeletal muscle cells

Bart Lagerwaard, Marjanne D. van der Hoek, Joris Hoeks, Lotte Grevendonk, Arie G. Nieuwenhuizen, Jaap Keijer, Vincent C.J. de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Protein acylation via metabolic acyl-CoA intermediates provides a link between cellular metabolism and protein functionality. A process in which acetyl-CoA and acetylation are fine-tuned is during myogenic differentiation. However, the roles of other protein acylations remain unknown. Protein propionylation could be functionally relevant because propionyl-CoA can be derived from the catabolism of amino acids and fatty acids and was shown to decrease during muscle differentiation. We aimed to explore the potential role of protein propionylation in muscle differentiation, by mimicking a pathophysiological situation with high extracellular propionate which increases propionyl-CoA and protein propionylation, rendering it a model to study increased protein propionylation. Exposure to extracellular propionate, but not acetate, impaired myogenic differentiation in C2C12 cells and propionate exposure impaired myogenic differentiation in primary human muscle cells. Impaired differentiation was accompanied by an increase in histone propionylation as well as histone acetylation. Furthermore, chromatin immunoprecipitation showed increased histone propionylation at specific regulatory myogenic differentiation sites of the Myod gene. Intramuscular propionylcarnitine levels are higher in old compared to young males and females, possibly indicating increased propionyl-CoA levels with age. The findings suggest a role for propionylation and propionyl-CoA in regulation of muscle cell differentiation and ageing, possibly via alterations in histone acylation.

Original languageEnglish
Article number111495
JournalMechanisms of Ageing and Development
Volume196
Early online date28 Apr 2021
DOIs
Publication statusPublished - 2021

Keywords

  • Aging
  • Histone acylation
  • Propionylation
  • Skeletal muscle differentiation

Fingerprint

Dive into the research topics of 'Propionate hampers differentiation and modifies histone propionylation and acetylation in skeletal muscle cells'. Together they form a unique fingerprint.

Cite this