Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts.
Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts.
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苹果酸酶偶联成骨细胞线粒体有氧糖酵解。
DOI：
10.1016/j.celrep.2020.108108
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发表时间：
2020-09-08
期刊：
影响因子：
8.8
通讯作者：
Long F
中科院分区：
文献类型：
--
作者：
Lee WC;Ji X;Nissim I;Long F
成骨细胞（主要的骨形成细胞）的代谢程序仍不完全清楚。在小鼠颅骨细胞中，我们确定有氧条件下成骨细胞的分化伴随着葡萄糖消耗和乳酸产生的显着增加，但耗氧量的减少。因此，有氧糖酵解约占成熟成骨细胞 ATP 产生的 80%。小鼠体内 13C 标记葡萄糖的体内示踪表明，骨中的葡萄糖很容易代谢为乳酸，但在 TCA 循环中不易代谢为有机酸。成骨细胞培养物中的葡萄糖示踪表明，丙酮酸被羧化，形成苹果酸-天冬氨酸穿梭不可或缺的苹果酸。 RNA 测序 (RNA-seq) 鉴定出 Me2，编码线粒体 NAD 依赖性苹果酸酶亚型，在成骨细胞分化过程中被特异性上调。 Me2 的敲低显着降低糖酵解通量并损害成骨细胞增殖和分化。因此，线粒体苹果酸酶在功能上将线粒体与成骨细胞中的有氧糖酵解结合起来。李等人。研究发现，即使在有氧条件下，成熟的成骨细胞也能通过糖酵解产生 80% 的能量。体内代谢追踪确定乳酸是葡萄糖在骨骼中的主要命运。苹果酸酶 2 和苹果酸-天冬氨酸穿梭机制支持强劲的糖酵解。
The metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen consumption. As a result, aerobic glycolysis accounts for approximately 80% of the ATP production in mature osteoblasts. In vivo tracing with 13C-labeled glucose in the mouse shows that glucose in bone is readily metabolized to lactate but not organic acids in the TCA cycle. Glucose tracing in osteoblast cultures reveals that pyruvate is carboxylated to form malate integral to the malate-aspartate shuttle. RNA sequencing (RNA-seq) identifies Me2, encoding the mitochondrial NAD-dependent isoform of malic enzyme, as being specifically upregulated during osteoblast differentiation. Knockdown of Me2 markedly reduces the glycolytic flux and impairs osteoblast proliferation and differentiation. Thus, the mitochondrial malic enzyme functionally couples the mitochondria with aerobic glycolysis in osteoblasts. Lee et al. discover that mature osteoblasts produce 80% of the energy from glycolysis even under aerobic conditions. In vivo metabolic tracing identifies lactate as the predominant fate of glucose in bone. The robust glycolysis is supported by malic enzyme 2 and the malate-aspartate shuttle.
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DOI：
10.1042/bj20120163
发表时间：
2012-06-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Nissim I;Horyn O;Nissim I;Daikhin Y;Wehrli SL;Yudkoff M;Matschinsky FM
通讯作者：
Matschinsky FM
影响因子：
4.1
作者：
ADAMEK, G;FELIX, R;FLEISCH, H
通讯作者：
FLEISCH, H
影响因子：
4.8
作者：
Nissim, Itzhak;Horyn, Oksana;Yudkoff, Marc
通讯作者：
Yudkoff, Marc
影响因子：
56.9
作者：
PECK, WA;BIRGE, SJ;FEDAK, SA
通讯作者：
FEDAK, SA
影响因子：
4.8
作者：
Chen, Hong;Ji, Xing;Long, Fanxin
通讯作者：
Long, Fanxin