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

10 Citations (Scopus)

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

Fingerprint

Carnitine O-Palmitoyltransferase
Lysine
Phosphopyruvate Hydratase
Isotope Labeling
Mutation
Proteins
Cell proliferation
Post Translational Protein Processing
Glutamine
Cell culture
Metabolism
Isotopes
Proteomics
Labeling
Cell Culture Techniques
Cells
Cell Proliferation

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)

Cite this

Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity. / Kurmi, Kiran; Hitosugi, Sadae; Wiese, Elizabeth K.; Boakye-Agyeman, Felix; Gonsalves, Wilson; Lou, Zhenkun; Karnitz, Larry M; Goetz, Matthew Philip; Hitosugi, Taro D.

In: Cell Reports, Vol. 22, No. 6, 06.02.2018, p. 1365-1373.

Research output: Contribution to journalArticle

Kurmi, Kiran ; Hitosugi, Sadae ; Wiese, Elizabeth K. ; Boakye-Agyeman, Felix ; Gonsalves, Wilson ; Lou, Zhenkun ; Karnitz, Larry M ; Goetz, Matthew Philip ; Hitosugi, Taro D. / Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity. In: Cell Reports. 2018 ; Vol. 22, No. 6. pp. 1365-1373.
@article{4642cb3a43e347b49cef0c4282b6c6e9,
title = "Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity",
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.",
keywords = "carnitine palmitoyltransferase 1A, CPT1A, lysine succinylation, lysine succinyltransferase, metabolism, post-translational modification, signal transduction, succinyl-CoA",
author = "Kiran Kurmi and Sadae Hitosugi and Wiese, {Elizabeth K.} and Felix Boakye-Agyeman and Wilson Gonsalves and Zhenkun Lou and Karnitz, {Larry M} and Goetz, {Matthew Philip} and Hitosugi, {Taro D}",
year = "2018",
month = "2",
day = "6",
doi = "10.1016/j.celrep.2018.01.030",
language = "English (US)",
volume = "22",
pages = "1365--1373",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity

AU - Kurmi, Kiran

AU - Hitosugi, Sadae

AU - Wiese, Elizabeth K.

AU - Boakye-Agyeman, Felix

AU - Gonsalves, Wilson

AU - Lou, Zhenkun

AU - Karnitz, Larry M

AU - Goetz, Matthew Philip

AU - Hitosugi, Taro D

PY - 2018/2/6

Y1 - 2018/2/6

N2 - 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.

AB - 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.

KW - carnitine palmitoyltransferase 1A

KW - CPT1A

KW - lysine succinylation

KW - lysine succinyltransferase

KW - metabolism

KW - post-translational modification

KW - signal transduction

KW - succinyl-CoA

UR - http://www.scopus.com/inward/record.url?scp=85041718240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041718240&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.01.030

DO - 10.1016/j.celrep.2018.01.030

M3 - Article

C2 - 29425493

AN - SCOPUS:85041718240

VL - 22

SP - 1365

EP - 1373

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -