Subbalakshmi Ayalur Raghu, Mirzapoiazova Tamara, Kulkarni Prakash, Salgia Ravi
Department of Medical Oncology, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA.
Department of Systems Biology, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA.
bioRxiv. 2025 May 19:2025.05.15.654228. doi: 10.1101/2025.05.15.654228.
In biology, oscillations are observed across a wide spectrum of processes and systems. Oscillatory systems are typically leveraged to transmit information within cells. However, they can also serve to transmit information between organisms underscoring their fundamental role in regulating transitions, maintaining stability, and responding to environmental stimuli. In this study, we explore mitochondrial fission and fusion dynamics through the framework of the Belousov-Zhabotinsky (BZ) reaction, a hallmark of non-equilibrium system that exhibits periodic changes in reactant concentrations through autocatalysis and feedback regulation. We observed that mitochondrial changes followed an oscillatory dynamic where the fission, fusion and intermediary factors undergo oscillations. Also, by modelling comparison with publicly available datasets of diseased condition before and after therapy, we observed similarities, where under diseased condition there is increased concentration of the fission and fusion factors but upon treatment the concentration of the intermediary factors increase. Also, patient survival data analysis showed that increase in fission and fusion factors correlated with increased deaths but when there is increase in the intermediary factor concentration, we see better patient survival. These results highlight the possibility of targeting mitochondrial dynamics as a potential strategy for therapeutic development for diseases such as cancer where mitochondrial dynamics is dysregulated.
在生物学中,振荡现象在广泛的过程和系统中都能观察到。振荡系统通常被用于在细胞内传递信息。然而,它们也可以在生物体之间传递信息,这突出了它们在调节转变、维持稳定性以及对环境刺激做出反应方面的基本作用。在本研究中,我们通过贝洛索夫-扎博廷斯基(BZ)反应的框架来探索线粒体的裂变和融合动态,BZ反应是非平衡系统的一个标志,它通过自催化和反馈调节使反应物浓度呈现周期性变化。我们观察到线粒体的变化遵循一种振荡动态,其中裂变、融合和中间因子都经历振荡。此外,通过与公开可用的疾病治疗前后数据集进行建模比较,我们观察到一些相似之处,即在疾病状态下裂变和融合因子的浓度增加,但治疗后中间因子的浓度增加。而且,患者生存数据分析表明,裂变和融合因子的增加与死亡人数增加相关,但当中间因子浓度增加时,患者的生存率更高。这些结果凸显了将线粒体动态作为一种潜在策略来开发针对线粒体动态失调疾病(如癌症)的治疗方法的可能性。