M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.
M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.
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DOI：
10.1371/journal.pone.0031815
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pomiès P
中科院分区：
文献类型：
--
作者：
Cambier L;Rassam P;Chabi B;Mezghenna K;Gross R;Eveno E;Auffray C;Wrutniak-Cabello C;Lajoix AD;Pomiès P
由于核或线粒体DNA改变导致的线粒体功能障碍导致多种疾病，如代谢性肌病、神经退行性疾病、糖尿病和癌症。然而，到目前为止，估计1500个线粒体蛋白质中只有一半被鉴定出来，其中大多数蛋白质的功能仍有待确定。在这里，我们描述了M19，一种新的线粒体核蛋白，在肌肉和胰腺β细胞中的功能。我们已经确定了位于M19 N端的一个13个长的氨基酸序列，该序列针对线粒体的蛋白质。此外，利用RNA干扰和过度表达策略，我们证明了M19调节线粒体的氧耗和ATP的产生，从而调节呼吸链的活性。为了确定M19是否在多种细胞活动的调节中发挥作用，我们发现这种核蛋白可能通过调节线粒体三磷酸腺苷的产生，作用于肌源性C2C12细胞的晚期肌肉分化，并在基础葡萄糖条件下对INS-1胰腺β-细胞的胰岛素分泌起允许作用。因此，我们的结果在线粒体类核蛋白和呼吸链活动的调节之间建立了功能联系，导致调节主要的细胞过程，如肌肉发生和胰岛素分泌。
Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.
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