Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity

Kiran Kurmi, Sadae Hitosugi, Elizabeth K. Wiese, Felix Boakye-Agyeman, Wilson Gonsalves, Zhenkun Lou, Larry M Karnitz, Matthew Philip Goetz, Taro D Hitosugi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Lysine succinylation was recently identified as a post-translational modification in cells. However, the molecular mechanism underlying lysine succinylation remains unclear. Here, we show that carnitine palmitoyltransferase 1A (CPT1A) has lysine succinyltransferase (LSTase) activity in vivo and in vitro. Using a stable isotope labeling by amino acid in cell culture (SILAC)-based proteomics approach, we found that 101 proteins were more succinylated in cells expressing wild-type (WT) CPT1A compared with vector control cells. One of the most heavily succinylated proteins in this analysis was enolase 1. We found that CPT1A WT succinylated enolase 1 and reduced enolase enzymatic activity in cells and in vitro. Importantly, mutation of CPT1A Gly710 (G710E) selectively inactivated carnitine palmitoyltransferase (CPTase) activity but not the LSTase activity that decreased enolase activity in cells and promoted cell proliferation under glutamine depletion. These findings suggest that CPT1A acts as an LSTase that can regulate enzymatic activity of a substrate protein and metabolism independent of its classical CPTase activity. Kurmi et al. find that carnitine palmitoyltransferase (CPT) 1A has lysine succinyltransferase (LSTase) activity in vivo and in vitro. Mutation of CPT1A Gly710 (G710E) selectively inactivates canonical carnitine palmitoyltransferase (CPTase) activity but not LSTase activity.

Original languageEnglish (US)
Pages (from-to)1365-1373
Number of pages9
JournalCell Reports
Volume22
Issue number6
DOIs
StatePublished - Feb 6 2018

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Keywords

  • carnitine palmitoyltransferase 1A
  • CPT1A
  • lysine succinylation
  • lysine succinyltransferase
  • metabolism
  • post-translational modification
  • signal transduction
  • succinyl-CoA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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