线粒体中的代谢感应和控制。
Metabolic sensing and control in mitochondria.
机构信息
Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
出版信息
Mol Cell. 2023 Mar 16;83(6):877-889. doi: 10.1016/j.molcel.2023.02.016.
Mitochondria are membrane-enclosed organelles with endosymbiotic origins, harboring independent genomes and a unique biochemical reaction network. To perform their critical functions, mitochondria must maintain a distinct biochemical environment and coordinate with the cytosolic metabolic networks of the host cell. This coordination requires them to sense and control metabolites and respond to metabolic stresses. Indeed, mitochondria adopt feedback or feedforward control strategies to restrain metabolic toxicity, enable metabolic conservation, ensure stable levels of key metabolites, allow metabolic plasticity, and prevent futile cycles. A diverse panel of metabolic sensors mediates these regulatory circuits whose malfunctioning leads to inborn errors of metabolism with mild to severe clinical manifestations. In this review, we discuss the logic and molecular basis of metabolic sensing and control in mitochondria. The past research outlined recurring patterns in mitochondrial metabolic sensing and control and highlighted key knowledge gaps in this organelle that are potentially addressable with emerging technological breakthroughs.
线粒体是具有内共生起源的膜包被细胞器，拥有独立的基因组和独特的生化反应网络。为了发挥其关键功能，线粒体必须维持独特的生化环境，并与宿主细胞的胞质代谢网络协调。这种协调需要它们感知和控制代谢物，并对代谢应激做出反应。事实上，线粒体采用反馈或前馈控制策略来抑制代谢毒性、实现代谢守恒、确保关键代谢物的稳定水平、允许代谢可塑性，并防止无效循环。一系列不同的代谢物传感器介导这些调节回路，其功能障碍导致从轻度到重度临床表现的先天性代谢错误。在这篇综述中，我们讨论了线粒体代谢感应和控制的逻辑和分子基础。过去的研究概述了线粒体代谢感应和控制中的重复模式，并强调了该细胞器中潜在的关键知识空白，这些空白可能通过新兴技术突破得到解决。
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