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Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production
Author(s) -
Chen Yan,
Cai Guo He,
Xia Bo,
Wang Xin,
Zhang Cong Cong,
Xie Bao Cai,
Shi Xiao Chen,
Liu Huan,
Lu Jun Feng,
Zhang Rui Xin,
Zhu Meng Qing,
Liu Min,
Yang Shi Zhen,
Yang Zhang Dan,
Chu Xin Yi,
Khan Rajwali,
Wang Yong Liang,
Wu Jiang Wei
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903224rr
Subject(s) - adipogenesis , lipogenesis , aconitase , mitochondrion , mitochondrial biogenesis , rotenone , biology , biochemistry , endocrinology , chemistry , microbiology and biotechnology , medicine , adipose tissue
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.