Mitochondrial fusion promoter M1, a cell-permeable phenylhydrazone, effectively promotes mitochondrial fusion[1]. Mitochondrial fusion promoter M1 exerts anti-inflammatory and antioxidant effects by regulating mitochondrial function and blocking the PI3K-AKT signaling pathway[2]. Mitochondrial fusion promoter M1 has been widely used in cell models to enhance the complementary mitochondrial metabolism[3].
In vitro, Mitochondrial fusion promoter M1 treatment for 24 hours induced the elongation of mitochondria in mitofusin 1-knockout mouse embryonic fibroblast (MEF) cells and mitofusin 2-knockout MEF cells, with EC50 values of 5.3μM and 4.42μM, respectively[4]. Treatment with 20μM of the Mitochondrial fusion promoter M1 for 3 days reduced the susceptibility of Jurkat cells to HIV infection, resulting in an increase in the oxygen consumption rate (OCR) of the cells and a decrease in the extracellular acidification rate (ECAR)[5]. Mitochondrial fusion promoter M1 treatment (1μM; 12h) alleviated the mitochondrial damage and fusion inhibition in triphenyl phosphate (TPHP)-induced TM3 cells, reducing the decline in cell viability and the increase in apoptosis rate induced by TPHP[6].
In vivo, Mitochondrial fusion promoter M1 treatment via continuous intraperitoneal injection at a dose of 2mg/kg/day for 6 weeks significantly promoted mitochondrial fusion in the heart tissue of diabetic rats, and weakened the decrease in the expression of optic nerve atrophy 1 (Opa1), alleviated oxidative stress, improved mitochondrial function, and alleviated dilated cardiomyopathy (DCM) in diabetic rats[7]. Intravenous injection of a single dose of Mitochondrial fusion promoter M1 (2mg/kg) 15 minutes before cardiac ischemia/reperfusion (I/R) injury alleviated the brain mitochondrial dysfunction, blood-brain barrier disruption, macrophage infiltration, apoptosis and the expression of Alzheimer's disease-related proteins in rats following cardiac I/R injury[8].
References:
[1] Asalla S, Girada S B, Kuna R S, et al. Restoring mitochondrial function: a small molecule-mediated approach to enhance glucose stimulated insulin secretion in cholesterol accumulated pancreatic beta cells[J]. Scientific Reports, 2016, 6(1): 27513.
[2] Zeng T, Liu L, Xu D, et al. The mitochondrial fusion promoter M1 mitigates cigarette smoke-induced airway inflammation and oxidative stress via the PI3K-AKT signaling pathway[J]. Lung, 2025, 203(1): 12.
[3] Yang L, Long Q, Liu J, et al. Mitochondrial fusion provides an ‘initial metabolic complementation’controlled by mtDNA[J]. Cellular and Molecular Life Sciences, 2015, 72(13): 2585-2598.
[4] Wang D, Wang J, Bonamy G M C, et al. A small molecule promotes mitochondrial fusion in mammalian cells[J]. Angewandte Chemie International Edition, 2012, 51(37): 9302-9305.
[5] Song Z, Wang J, Zheng Z, et al. Mitochondrial fusion reduces T cell susceptibility to HIV infection through citrate modulation[J]. Journal of Leukocyte Biology, 2025, 117(5): qiaf042.
[6] Wang M, Xu J, Zhao Z, et al. Triphenyl phosphate induced apoptosis of mice testicular Leydig cells and TM3 cells through ROS-mediated mitochondrial fusion inhibition[J]. Ecotoxicology and Environmental Safety, 2023, 256: 114876.
[7] Ding M, Liu C, Shi R, et al. Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way[J]. Acta Physiologica, 2020, 229(1): e13428.
[8] Surinkaew P, Apaijai N, Sawaddiruk P, et al. Mitochondrial fusion promoter alleviates brain damage in rats with cardiac ischemia/reperfusion injury[J]. Journal of Alzheimer’s Disease, 2020, 77(3): 993-1003.
Mitochondrial fusion promoter M1是一种具有细胞渗透性的苯腙类化合物，能有效促进线粒体融合[1]。Mitochondrial fusion promoter M1通过调节线粒体功能并阻断PI3K-AKT信号通路，发挥抗炎和抗氧化作用[2]。Mitochondrial fusion promoter M1已在细胞模型中广泛用于增强互补性线粒体代谢[3]。
在体外，在体外，Mitochondrial fusion promoter M1处理 24 小时诱导mitofusin 1敲除小鼠胚胎成纤维细胞（MEF）和mitofusin 2敲除MEF细胞的线粒体伸长，EC50值分别为5.3μM和4.42μM[4]。用20μM的Mitochondrial fusion promoter M1处理3天降低了Jurkat细胞对HIV感染的易感性，导致细胞耗氧率（OCR）增加和细胞外酸化率（ECAR）降低[5]。Mitochondrial fusion promoter M1处理（1μM；12小时）减轻了triphenyl phosphate（TPHP）诱导的TM3细胞中的线粒体损伤和融合抑制，减少了TPHP诱导的细胞活力下降和凋亡率增加[6]。
在体内，Mitochondrial fusion promoter M1以2mg/kg/day的剂量连续腹腔注射 6 周，显著促进了糖尿病大鼠心脏组织中的线粒体融合，减弱了optic nerve atrophy 1（Opa1）表达的下降，减轻了氧化应激，改善了线粒体功能，并缓解了糖尿病大鼠的扩张型心肌病（DCM）[7]。在心脏缺血/再灌注（I/R）损伤前15 分钟静脉注射单剂量的Mitochondrial fusion promoter M1（2mg/kg）缓解了心脏I/R损伤后大鼠的脑线粒体功能障碍、血脑屏障破坏、巨噬细胞浸润、细胞凋亡和阿尔茨海默病相关蛋白的表达[8]。