Hood David A, Adhihetty Peter J, Colavecchia Marco, Gordon Joseph W, Irrcher Isabella, Joseph Anna-Maria, Lowe Sabena T, Rungi Arne A
School of Kinesiology and Health Science, Department of Biology, York University, Toronto, Ontario, Canada.
Med Sci Sports Exerc. 2003 Jan;35(1):86-94. doi: 10.1097/00005768-200301000-00015.
The importance of the mitochondrial protein import pathway, discussed relative to other steps involved in the overall biogenesis of the organelle, are reviewed.
Mitochondrial biogenesis is a product of complex interactions between the nuclear and mitochondrial genomes. Signaling pathways, such as those activated by exercise, initiate the activation of transcription factors that increase the production of mRNA from nuclear and mitochondrial DNA. Nuclear gene products are translated in the cytosol as precursor proteins with inherent targeting signals. These precursor proteins interact with molecular chaperones that direct them to the import machinery of the outer membrane (Tom complex). The precursor is unfolded and transferred through the outer membrane, across the intermembrane space to the mitochondrial inner membrane translocases (Tim complex). Intramitochondrial components (mtHSP70) pull the precursor into the matrix, cleave off the targeting sequence (mitochondrial processing peptidase), and refold the protein (HSP60, cpn10) into its mature conformation. Physiological stressors such as contractile activity and thyroid hormone accelerate protein import into the mitochondria, coincident with an increase in the expression of some components of the import machinery. This is important for the overall expansion of the mitochondrial reticulum. Conversely, impairments in the import process can be a cause of mitochondrial dysfunction and disease.
Efforts to further characterize the components of the import machinery, to define the role of specific machinery components on the import rate, and to examine protein import function in a variety of mitochondrial diseases are warranted.
回顾线粒体蛋白质输入途径的重要性，并与该细胞器整体生物发生过程中的其他步骤进行比较讨论。
线粒体生物发生是核基因组与线粒体基因组复杂相互作用的产物。信号通路，如运动激活的那些通路，启动转录因子的激活，从而增加核DNA和线粒体DNA的mRNA产生。核基因产物在细胞质中作为具有内在靶向信号的前体蛋白进行翻译。这些前体蛋白与分子伴侣相互作用，分子伴侣将它们导向外膜的输入机制（Tom复合体）。前体蛋白解折叠并穿过外膜，通过膜间隙到达线粒体内膜转位酶（Tim复合体）。线粒体内的成分（mtHSP70）将前体蛋白拉进基质，切除靶向序列（线粒体加工肽酶），并将蛋白质（HSP60、cpn10）重新折叠成其成熟构象。诸如收缩活动和甲状腺激素等生理应激源会加速蛋白质向线粒体的输入，同时输入机制的一些成分的表达也会增加。这对线粒体网络的整体扩展很重要。相反，输入过程的受损可能是线粒体功能障碍和疾病的一个原因。
有必要进一步表征输入机制的成分，确定特定机制成分对输入速率的作用，并研究各种线粒体疾病中的蛋白质输入功能。
