Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity.
Acetylation is one of the most crucial post-translational modifications that affect protein function. Protein lysine acetylation is catalyzed by acetyltransferases, and acetyl-CoA functions as the source of the acetyl group. Additionally, acetyl-CoA plays critical roles in maintaining the balance between carbohydrate metabolism and fatty acid synthesis. Here, we sought to determine whether lysine acetylation is an important process for adipocyte differentiation. Based on an analysis of the acetylome during adipogenesis, various proteins displaying significant quantitative changes were identified by LC-MS/MS. Of these identified proteins, we focused on malate dehydrogenase 1 (MDH1). The acetylation level of MDH1 was increased up to 6-fold at the late stage of adipogenesis. Moreover, overexpression of MDH1 in 3T3-L1 preadipocytes induced a significant increase in the number of cells undergoing adipogenesis. The introduction of mutations to putative lysine acetylation sites showed a significant loss of the ability of cells to undergo adipogenic differentiation. Furthermore, the acetylation of MDH1 dramatically enhanced its enzymatic activity and subsequently increased the intracellular levels of NADPH. These results clearly suggest that adipogenic differentiation may be regulated by the acetylation of MDH1 and that the acetylation of MDH1 is one of the cross-talk mechanisms between adipogenesis and the intracellular energy level.
Department of Biological Sciences,  KAIST, Daejeon 305-701,  Republic of Korea.
Eun Young
EY
Kim
Won Kon
WK
Kim
Hyo Jin
HJ
Kang
Jeong-Hoon
JH
Kim
Sang J
SJ
Chung
Yeon Soo
YS
Seo
Sung Goo
SG
Park
Sang Chul
SC
Lee
Kwang-Hee
KH
Bae
D041721:3T3-L1 Cells; D000107:Acetylation; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009249:NADP / Q000378:metabolism
D009249:NADP; D008291:Malate Dehydrogenase; D008239:Lysine