Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Curr Biol. 2022 Jun 20;32(12):R684-R696. doi: 10.1016/j.cub.2022.04.071.
Maintaining nutrient and energy homeostasis is crucial for the survival and function of cells and organisms in response to environmental stress. Cells have evolved a stress-induced catabolic pathway, termed autophagy, to adapt to stress conditions such as starvation. During autophagy, damaged or non-essential cellular structures are broken down in lysosomes, and the resulting metabolites are reused for core biosynthetic processes or energy production. Recent studies have revealed that autophagy can target and degrade different types of nutrient stores and produce a variety of metabolites and fuels, including amino acids, nucleotides, lipids and carbohydrates. Here, we will focus on how autophagy functions to balance cellular nutrient and energy demand and supply - specifically, how energy deprivation switches on autophagic catabolism, how autophagy halts anabolism by degrading the protein synthesis machinery, and how bulk and selective autophagy-derived metabolites recycle and feed into a variety of bioenergetic and anabolic pathways during stress conditions. Recent new insights and progress in these areas provide a better understanding of how resource mobilization and reallocation sustain essential metabolic and anabolic activities under unfavorable conditions.
维持营养和能量平衡对于细胞和生物体在应对环境压力时的生存和功能至关重要。细胞已经进化出一种应激诱导的分解代谢途径,称为自噬,以适应饥饿等应激条件。在自噬过程中,受损或非必需的细胞结构在溶酶体中被分解,产生的代谢物被重新用于核心生物合成过程或能量产生。最近的研究表明,自噬可以靶向和降解不同类型的营养物质储存,并产生多种代谢物和燃料,包括氨基酸、核苷酸、脂质和碳水化合物。在这里,我们将重点关注自噬如何平衡细胞的营养和能量需求和供应——具体来说,能量剥夺如何启动自噬分解代谢,自噬如何通过降解蛋白质合成机制来阻止合成代谢,以及大量和选择性自噬衍生的代谢物如何在应激条件下循环并进入各种生物能量和合成代谢途径。这些领域的最新新见解和进展提供了对资源动员和重新分配如何在不利条件下维持基本代谢和合成代谢活动的更好理解。