Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production

被引：19

作者：

Chen Yan ^{[1
]}

Cai Guo He ^{[1
]}

Xia Bo ^{[1
]}

Wang Xin ^{[1
]}

Zhang Cong Cong ^{[1
]}

Xie Bao Cai ^{[1
]}

Shi Xiao Chen ^{[1
]}

Liu Huan ^{[1
]}

Lu Jun Feng ^{[1
]}

Zhang Rui Xin ^{[1
]}

Zhu Meng Qing ^{[1
]}

Liu Min ^{[1
]}

Yang Shi Zhen ^{[1
]}

Yang Zhang Dan ^{[1
]}

Chu Xin Yi ^{[1
]}

Khan, Rajwali ^{[1
]}

Wang Yong Liang ^{[1
]}

Wu Jiang Wei ^{[1
]}

机构：

[1] Northwest A&F Univ, Key Lab Anim Genet Breeding & Reprod Shaanxi Prov, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China

来源：

FASEB JOURNAL | 2020年 / 34卷 / 05期

关键词：

cell differentiation; mitochondrial metabolism; TCA cycle; TRICARBOXYLIC-ACID CYCLE; WHITE ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; DYSFUNCTION; BIOGENESIS; OBESITY; MICE; LIPOGENESIS; DEFICIENCY; METABOLISM;

D O I：

10.1096/fj.201903224RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy.

引用

页码：6688 / 6702

页数：15

共 56 条

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