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Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2020-03-27)
Yan Chen, Guo He Cai, Bo Xia, Xin Wang, Cong Cong Zhang, Bao Cai Xie, Xiao Chen Shi, Huan Liu, Jun Feng Lu, Rui Xin Zhang, Meng Qing Zhu, Min Liu, Shi Zhen Yang, Dan Yang Zhang, Xin Yi Chu, Rajwali Khan, Yong Liang Wang, Jiang Wei Wu
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dexamethasone, powder, BioReagent, suitable for cell culture, ≥97%
Sigma-Aldrich
Rotenone, ≥95%
SAFC
Insulin, Human Recombinant, for research or for further manufacturing use, dry powder
Sigma-Aldrich
3-Isobutyl-1-methylxanthine, ≥99%, BioUltra
Sigma-Aldrich
Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, ≥98% (TLC), powder