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
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
收藏
页码:6688 / 6702
页数:15
相关论文
共 56 条
[1]   Hepatic Stearoyl-CoA desaturase-1 deficiency-mediated activation of mTORC1-PGC-1α axis regulates ER stress during high-carbohydrate feeding [J].
Aljohani, Ahmed ;
Khan, Mohammad Imran ;
Syed, Deeba N. ;
Abram, Bonneville ;
Lewis, Sarah ;
Neill, Lucas O' ;
Mukhtar, Hasan ;
Ntambi, James M. .
SCIENTIFIC REPORTS, 2019, 9 (1)
[2]   Cells Lacking the Fumarase Tumor Suppressor Are Protected from Apoptosis through a Hypoxia-Inducible Factor-Independent, AMPK-Dependent Mechanism [J].
Bardella, Chiara ;
Olivero, Martina ;
Lorenzato, Annalisa ;
Geuna, Massimo ;
Adam, Julie ;
O'Flaherty, Linda ;
Rustin, Pierre ;
Tomlinson, Ian ;
Pollard, Patrick J. ;
Di Renzo, Maria Flavia .
MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (15) :3081-3094
[3]   High plasma apolipoprotein B identifies obese subjects who best ameliorate white adipose tissue dysfunction and glucose-induced hyperinsulinemia after a hypocaloric diet [J].
Bissonnette, Simon ;
Saint-Pierre, Nathalie ;
Lamantia, Valerie ;
Leroux, Catherine ;
Provost, Viviane ;
Cyr, Yannick ;
Rabasa-Lhoret, Remi ;
Faraj, May .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2018, 108 (01) :62-76
[4]   ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia [J].
Bouwkamp, Christian G. ;
Afawi, Zaid ;
Fattal-Valevski, Aviva ;
Krabbendam, Inge E. ;
Rivetti, Stefano ;
Masalha, Rafik ;
Quadri, Marialuisa ;
Breedveld, Guido J. ;
Mandel, Hanna ;
Abu Tailakh, Muhammad ;
Beverloo, H. Berna ;
Stevanin, Giovanni ;
Brice, Alexis ;
van IJcken, Wilfred F. J. ;
Vernooij, Meike W. ;
Dolga, Amalia M. ;
de Vrij, Femke M. S. ;
Bonifati, Vincenzo ;
Kushner, Steven A. .
NEUROLOGY-GENETICS, 2018, 4 (02)
[5]   Assessing mitochondrial dysfunction in cells [J].
Brand, Martin D. ;
Nicholls, David G. .
BIOCHEMICAL JOURNAL, 2011, 435 :297-312
[6]   Altered Aconitase 2 Activity in Huntington's Disease Peripheral Blood Cells and Mouse Model Striatum [J].
Chen, Chiung-Mei ;
Wu, Yih-Ru ;
Chang, Kuo-Hsuan .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (11)
[7]   Mitochondria are impaired in the adipocytes of type 2 diabetic mice [J].
Choo, HJ ;
Kim, JH ;
Kwon, OB ;
Lee, CS ;
Mun, JY ;
Han, SS ;
Yoon, YS ;
Yoon, G ;
Choi, KM ;
Ko, YG .
DIABETOLOGIA, 2006, 49 (04) :784-791
[8]   ATM is activated by ATP depletion and modulates mitochondrial function through NRF1 [J].
Chow, Hei-Man ;
Cheng, Aifang ;
Song, Xuan ;
Swerdel, Mavis R. ;
Hart, Ronald P. ;
Herrup, Karl .
JOURNAL OF CELL BIOLOGY, 2019, 218 (03) :909-928
[9]   Metabolic remodeling of white adipose tissue in obesity [J].
Cummins, Timothy D. ;
Holden, Candice R. ;
Sansbury, Brian E. ;
Gibb, Andrew A. ;
Shah, Jasmit ;
Zafar, Nagma ;
Tang, Yunan ;
Hellmann, Jason ;
Rai, Shesh N. ;
Spite, Matthew ;
Bhatnagar, Aruni ;
Hill, Bradford G. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2014, 307 (03) :E262-E277
[10]   Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-α [J].
Dahlman, Ingrid ;
Forsgren, Margaretha ;
Sjogren, Annelie ;
Nordstrom, Elisabet Arvidsson ;
Kaaman, Maria ;
Naslund, Erik ;
Attersand, Anneli ;
Arner, Peter .
DIABETES, 2006, 55 (06) :1792-1799