4.5 Review

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

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 27, Issue 7, Pages 906-919

Publisher

WILEY
DOI: 10.1111/jcmm.17696

Keywords

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

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The mitochondrial-associated membrane (MAM) is a platform that promotes communication between the endoplasmic reticulum (ER) and mitochondria. It plays a crucial role in various physiological processes and its dysregulation can impact cancer cell fate. This review summarizes the structure of MAM and the functions of MAM-resident proteins in tumorigenesis, and discusses the mechanisms by which natural compounds induce cancer cell apoptosis through ER stress.
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.

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