The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression

Maohui Yang; Xuemei Qin; Xiaojie Liu

doi:10.1016/j.neubiorev.2025.106087

The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression

Neurosci Biobehav Rev. 2025 May:172:106087. doi: 10.1016/j.neubiorev.2025.106087. Epub 2025 Mar 1.

Authors

Maohui Yang¹, Xuemei Qin², Xiaojie Liu³

Affiliations

¹ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China.
² Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China. Electronic address: qinxm@sxu.edu.cn.
³ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan, Shanxi 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China. Electronic address: liuxiaojie@sxu.edu.cn.

PMID: 40031998
DOI: 10.1016/j.neubiorev.2025.106087

Abstract

Depression is a prevalent mental disorder with high morbidity and mortality and its pathogenesis remains exactly unclarified. However, mitochondria and endoplasmic reticulum (ER) are two highly dynamic organelles that perform an indispensable role in the development of depression. Mitochondrial dysfunction and ER stress are recognized as vital pathological hallmarks in depression. The changes of intracellular activities such as mitochondrial dynamics, mitophagy, energy metabolism and ER stress are closely correlated with the progression of depression. Moreover, organelles interactions are conducive to homeostasis and cellular functions, and mitochondrial-associated endoplasmic reticulum membranes (MAMs) serve as signaling hubs of the two organelles and the coupling of the pathological progression. The main roles of MAMs are involved in metabolism, signal transduction, lipid transport, and maintenance of its structure and function. At present, accumulating studies elucidated that MAMs have gradually become a novel therapeutic target in treatment of depression. In the review, we focus on influence of mitochondria dysfunction and ER stress on depression. Furthermore, we discuss the underlying role of MAMs in depression and highlight natural products targeting MAMs as potential antidepressants to treat depression.

Keywords: Depression; Endoplasmic reticulum; MAMs; Membranes couplings; Mitochondria; Natural products.

Publication types

Review

MeSH terms

Animals
Antidepressive Agents* / pharmacology
Depression* / drug therapy
Depression* / metabolism
Depressive Disorder* / drug therapy
Depressive Disorder* / metabolism
Endoplasmic Reticulum Stress* / drug effects
Endoplasmic Reticulum Stress* / physiology
Endoplasmic Reticulum* / drug effects
Endoplasmic Reticulum* / metabolism
Humans
Mitochondria* / drug effects
Mitochondria* / metabolism

Substances

Antidepressive Agents