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多功能细胞器线粒体参与细胞死亡、增殖及疾病过程。

A multi-functional organelle mitochondrion is involved in cell death, proliferation and disease.

作者信息

Ohta Shigeo

机构信息

Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-city, Nakagawa-pref., 211-8533 Japan.

出版信息

Curr Med Chem. 2003 Dec;10(23):2485-94. doi: 10.2174/0929867033456440.

Abstract

The mitochondrion, long considered an organelle specific to energy metabolism, is in fact multi-functional and involved in many diseases. Mitochondrial DNA accumulates somatic mutations during aging, the progression of cancer and diabetes. Most cancer cells contain homoplasmic mutations in the mitochondrial genome. Although little is known about the contributions of mutations to carcinogenesis, some mutations in the nuclear genes encoding mitochondrial proteins have been identified as responsible for certain familial cancers. Mitochondria play an essential role in generating the germ line by releasing mitochondrial ribosomal RNAs, by which the germ line transfers the genetic information necessary for life to the next generation. Collaboration between mitochondria and the cytosol occurs in several metabolic pathways. Many enzymes involved in synthesizing uridine, heme and steroids and in the urea cycle are located inside mitochondria. Notably, a reaction involved in the synthesis of UMP is coupled with the energized state of mitochondria. Thus, the synthesis of DNA and RNA should be indirectly coupled with the energized state of mitochondria. Additionally, storing calcium is an important role of mitochondria. Calcium functions as a second messenger in signal transduction, however, it also activates several proteinases or lipases to induce damage. The mitochondrion plays a significant role in necrosis and is a center for apoptosis, determining its initiation, regulation and execution. Thus, the mitochondrion is widely involved in cell proliferation, cell death and disease.

摘要

线粒体长期以来被认为是一种专门负责能量代谢的细胞器,实际上它具有多种功能,并与许多疾病相关。线粒体DNA在衰老、癌症进展和糖尿病过程中会积累体细胞突变。大多数癌细胞的线粒体基因组中存在同质突变。尽管对于突变在致癌过程中的作用了解甚少,但一些编码线粒体蛋白的核基因中的突变已被确定为某些家族性癌症的病因。线粒体在通过释放线粒体核糖体RNA产生生殖细胞的过程中发挥着至关重要的作用,通过这种方式生殖细胞将生命所需的遗传信息传递给下一代。线粒体与细胞质之间的协作发生在多种代谢途径中。许多参与尿苷、血红素和类固醇合成以及尿素循环的酶都位于线粒体内。值得注意的是,UMP合成过程中的一个反应与线粒体的能量状态相关。因此,DNA和RNA的合成应该间接与线粒体的能量状态相关。此外,储存钙是线粒体的一项重要功能。钙在信号转导中作为第二信使发挥作用,然而,它也会激活多种蛋白酶或脂肪酶从而导致损伤。线粒体在坏死过程中起重要作用,并且是细胞凋亡的中心,决定着细胞凋亡的起始、调控和执行。因此,线粒体广泛参与细胞增殖、细胞死亡和疾病过程。

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