Jakowec Nicolaus, Finkel Steven E
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, USA.
J Bacteriol. 2025 May 22;207(5):e0054224. doi: 10.1128/jb.00542-24. Epub 2025 Mar 31.
Bacterial energy-spilling pathways-such as overflow metabolism and futile cycles-have been considered inefficient forms of metabolism that result from poor regulatory control or function as mechanisms to cope with excess energy. However, mounting evidence places these seemingly wasteful reactions at the fulcrum between metabolic signaling and stress adaptation in bacteria. Specifically, energy-spilling pathways may mediate the metabolic reprogramming observed when cells encounter growth-limiting constraints (i.e., nutrient limitation). Recent insights spotlight microbial metabolism as an intricate signaling network that coordinates physiological programming with energy and nutrient conditions. Such intracellular metabolic cross stalk is pivotal to survival in competitive, fluctuating environments that bacteria frequently encounter in nature. In light of this paradigm of metabolic signaling, energy-spilling pathways are increasingly recognized as regulatory strategies that enable metabolic rewiring in response to stress. Overflow metabolism or futile cycles may generate secondary metabolites with signaling properties, alter the flux of metabolic pathways and the rate of nutrient acquisition, or stimulate regulatory nodes to trigger specific metabolic programs in response to environmental challenges. Furthermore, the observation of such expensive pathways under laboratory conditions purported to be "energy limiting" may in fact suggest energy sufficiency, compelling us to rethink how we model energy limitation and starvation for bacteria.
细菌的能量溢出途径，如溢流代谢和无效循环，一直被认为是低效的代谢形式，是由不良的调节控制导致的，或者作为应对过量能量的机制。然而，越来越多的证据表明，这些看似浪费的反应处于细菌代谢信号传导和应激适应的支点位置。具体而言，能量溢出途径可能介导细胞在遇到生长限制因素（即营养限制）时所观察到的代谢重编程。最近的见解将微生物代谢视为一个复杂的信号网络，该网络将生理程序与能量和营养状况协调起来。这种细胞内的代谢交叉联系对于细菌在自然界中经常遇到的竞争性、波动环境中的生存至关重要。根据这种代谢信号传导的范式，能量溢出途径越来越被认为是一种调节策略，能够使代谢在应激时重新布线。溢流代谢或无效循环可能产生具有信号特性的次生代谢产物，改变代谢途径的通量和营养获取速率，或刺激调节节点以触发特定的代谢程序来应对环境挑战。此外，在所谓“能量受限”的实验室条件下观察到这些代价高昂的途径，实际上可能表明能量充足，这促使我们重新思考如何为细菌建立能量限制和饥饿的模型。
