Truong Thi Thuy, Singh Alka Ashok, Bang Nguyen Van, Vu Nguyen Minh Hung, Na Sungsoo, Choi Jaeyeop, Oh Junghwan, Mondal Sudip
Industry 4.0 Convergence Bionics Engineering, Department of Biomedical Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Department of Life Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Membranes (Basel). 2025 Aug 31;15(9):263. doi: 10.3390/membranes15090263.
Mitochondria-associated membranes (MAMs) are essential for cellular homeostasis. MAMs are specialized contact sites located between the endoplasmic reticulum (ER) and mitochondria and control apoptotic pathways, lipid metabolism, autophagy initiation, and calcium signaling, processes critical to the survival and function of neurons. Although this area of membrane biology remains understudied, increasing evidence links MAM dysfunction to the etiology of major neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). MAMs consist of a network of protein complexes that mediate molecular exchange and ER-mitochondria tethering. MAMs regulate lipid flow in the brain, including phosphatidylserine and cholesterol; disruption of this process causes membrane instability and impaired synaptic function. Inositol 1,4,5-trisphosphate receptor-voltage-dependent anion channel 1 (IP3R-VDAC1) interactions at MAMs maintain calcium homeostasis, which is required for mitochondria to produce ATP; dysregulation promotes oxidative stress and neuronal death. An effective therapeutic approach for altering neurodegenerative processes is to restore the functional integrity of MAMs. Improving cell-to-cell interactions and modulating MAM-associated proteins may contribute to the restoration of calcium homeostasis and lipid metabolism, both of which are key for neuronal protection. MAMs significantly contribute to the progression of neurodegenerative diseases, making them promising targets for future therapeutic research. This review emphasizes the increasing importance of MAMs in the study of neurodegeneration and their potential as novel targets for membrane-based therapeutic interventions.
线粒体相关膜（MAMs）对细胞内稳态至关重要。MAMs是位于内质网（ER）和线粒体之间的特殊接触位点，控制细胞凋亡途径、脂质代谢、自噬起始和钙信号传导，这些过程对神经元的存活和功能至关重要。尽管这一膜生物学领域仍未得到充分研究，但越来越多的证据表明MAM功能障碍与主要神经退行性疾病如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症（ALS）的病因有关。MAMs由介导分子交换和内质网-线粒体连接的蛋白质复合物网络组成。MAMs调节大脑中的脂质流动，包括磷脂酰丝氨酸和胆固醇；这一过程的破坏会导致膜不稳定和突触功能受损。MAMs处的肌醇1,4,5-三磷酸受体-电压依赖性阴离子通道1（IP3R-VDAC1）相互作用维持钙稳态，这是线粒体产生ATP所必需的；失调会促进氧化应激和神经元死亡。改变神经退行性过程的一种有效治疗方法是恢复MAMs的功能完整性。改善细胞间相互作用和调节与MAM相关的蛋白质可能有助于恢复钙稳态和脂质代谢，这两者都是神经元保护的关键。MAMs对神经退行性疾病的进展有显著影响，使其成为未来治疗研究的有希望的靶点。本综述强调了MAMs在神经退行性变研究中的重要性日益增加及其作为基于膜的治疗干预新靶点的潜力。
