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ATP Citrate Lyase Regulates Myofiber Differentiation and Increases Regeneration by Altering Histone Acetylation.

Abstract：

:ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression. ACL overexpression in murine skeletal muscle leads to improved regeneration after cardiotoxin-mediated damage. Thus, our findings suggest a mechanism for regulating SC differentiation and enhancing regeneration, which might be exploited for devising therapeutic approaches for treating skeletal muscle disease.

journal_name

Cell Rep

journal_title

Cell reports

authors

Das S,Morvan F,Morozzi G,Jourde B,Minetti GC,Kahle P,Rivet H,Brebbia P,Toussaint G,Glass DJ,Fornaro M

doi

10.1016/j.celrep.2017.11.038

subject

Has Abstract

pub_date

2017-12-12 00:00:00

pages

3003-3011

issue

11

issn

2211-1247

pii

S2211-1247(17)31675-3

journal_volume

21

pub_type

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