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Review
. 2023 Apr;27(7):906-919.
doi: 10.1111/jcmm.17696. Epub 2023 Feb 27.

Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer

Xi Yang  1   2 , Jing Zhuang  1   2 , Weilong Song  1   2 , Wangjie Shen  1   2 , Wei Wu  1   2 , Hong Shen  1   3 , Shuwen Han  1   2   3
Affiliations
Review

Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer

Xi Yang et al. J Cell Mol Med. 2023 Apr.

Abstract

The mitochondrial-associated membrane (MAM) is a physical platform that facilitates communication between the endoplasmic reticulum (ER) and mitochondria. It is enriched with many proteins and enzymes and plays an important role in the regulation of several fundamental physiological processes, such as calcium (Ca2+ ) transfer, lipid synthesis, cellular autophagy and ER stress. Accumulating evidence suggests that oncogenes and suppressor genes are present at the ER-mitochondrial contact site, and their alterations can affect Ca2+ flux, lipid homeostasis, and the dysregulation of mitochondrial dynamics, thereby influencing the fate of cancer cells. Understanding the fundamental role of MAM-resident proteins in tumorigenesis could support the search for novel therapeutic targets in cancer. In this review, we summarize the basic structure of MAM and the core functions of MAM-resident proteins in tumorigenesis. In addition, we discuss the mechanisms by which natural compounds promote cancer cell apoptosis from the perspective of ER stress.

Keywords: ER stress; autophagy; calcium transfer; cancer; endoplasmic reticulum; lipid synthesis; mitochondria; mitochondrial-associated membrane.

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Conflict of interest statement

The authors declare that no potential conflicts of interest exist.

Figures

FIGURE 1
FIGURE 1
Schematic summary of key MAM‐resident proteins involved in ER‐mitochondria Ca2+ transfer, lipid metabolism, autophagy and ER stress. ER, endoplasmic reticulum; MAM, mitochondrial‐associated membrane.
FIGURE 2
FIGURE 2
Schematic model of the ERMES complex. ERMES is composed of five subunits, including the mitochondrial outer membrane protein Mdm10, ER‐resident protein Mmm1, and three peripheral membrane proteins, namely Mdm34, Mdm1 and Gem1. ER, endoplasmic reticulum; ERMES, endoplasmic reticulum and mitochondria encounter structures.
FIGURE 3
FIGURE 3
Natural compounds or MAM‐related proteins induce apoptosis associated with endoplasmic reticulum stress via the mitochondrial pathway to affect the nature of cancer.
See this image and copyright information in PMC

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