Carnitine o-octanoyltransferase is a p53 target that promotes oxidative metabolism and cell survival following nutrient starvation.
Carnitine o-octanoyltransferase is a p53 target that promotes oxidative metabolism and cell survival following nutrient starvation.
复制标题
肉碱O- o-octanoyltransferase是一个p53靶标，可在营养饥饿后促进氧化代谢和细胞存活。
DOI：
10.1016/j.jbc.2023.104908
复制
发表时间：
2023-07
影响因子：
4.8
通讯作者：
Zhang, Yanping
中科院分区：
文献类型：
--
作者：
Sanford, Jack D.;Franklin, Derek;Grois, Gabriella A.;Jin, Aiwen;Zhang, Yanping
虽然已知P53广泛调节细胞代谢，但调节这一调节的特定活动仍有部分了解。在这里，我们确定肉碱o-辛酰基转移酶(CROT)是一种P53反式激活靶点，它是以依赖于P53的方式被细胞应激上调的。CROT是一种过氧酶，催化超长链脂肪酸转化为中链脂肪酸，在β氧化过程中可被线粒体吸收。P53通过与CROT基因5‘端非编码区中的共同反应元件结合来诱导CROT转录。WT的过表达但不是酶失活的突变CROT促进线粒体的氧化呼吸，而CROT的下调抑制线粒体的氧化呼吸。营养耗竭诱导依赖于p53的CROT表达，促进细胞生长和存活；相反，在营养耗竭期间，缺乏CROT的细胞会钝化细胞生长并降低存活率。总而言之，这些数据与一个模型一致，在该模型中，P53调控的CROT表达使细胞能够更有效地利用储存的超长链脂肪酸来生存营养枯竭压力。
Whereas it is known that p53 broadly regulates cell metabolism, the specific activities that mediate this regulation remain partially understood. Here, we identified carnitine o-octanoyltransferase (CROT) as a p53 transactivation target that is upregulated by cellular stresses in a p53-dependent manner. CROT is a peroxisomal enzyme catalyzing very long-chain fatty acids conversion to medium chain fatty acids that can be absorbed by mitochondria during β-oxidation. p53 induces CROT transcription through binding to consensus response elements in the 5′-UTR of CROT mRNA. Overexpression of WT but not enzymatically inactive mutant CROT promotes mitochondrial oxidative respiration, while downregulation of CROT inhibits mitochondrial oxidative respiration. Nutrient depletion induces p53-dependent CROT expression that facilitates cell growth and survival; in contrast, cells deficient in CROT have blunted cell growth and reduced survival during nutrient depletion. Together, these data are consistent with a model where p53-regulated CROT expression allows cells to be more efficiently utilizing stored very long-chain fatty acids to survive nutrient depletion stresses.
登录
查看更多内容
DOI：
10.1196/annals.1320.002
发表时间：
2004-01-01
期刊：
CARNITINE: THE SCIENCE BEHIND A CONDITIONALLY ESSENTIAL NUTRIENT
影响因子：
--
作者：
Jogl, G;Hsiao, YS;Tong, L
通讯作者：
Tong, L
影响因子：
5.6
作者：
Krstic J;Reinisch I;Schupp M;Schulz TJ;Prokesch A
通讯作者：
Prokesch A
影响因子：
16
作者：
Jones, RG;Plas, DR;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
6.5
作者：
Lasheras-Otero, Irene;Feliu, Iker;Arozarena, Imanol
通讯作者：
Arozarena, Imanol
影响因子：
20.1
作者：
Park JY;Wang PY;Matsumoto T;Sung HJ;Ma W;Choi JW;Anderson SA;Leary SC;Balaban RS;Kang JG;Hwang PM
通讯作者：
Hwang PM