Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy

• Published in: Experimental & Molecular Medicine Vol. 56; no. 1; pp. 40 - 50
• Main Authors: An, Garam, Park, Junho, Song, Jisoo, Hong, Taeyeon, Song, Gwonhwa, Lim, Whasun
• Format: Journal Article
• Language: English
• Published: London Springer Science and Business Media LLC 01.02.2024; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 631/80/304; 631/80/86/2366; 96/2; 96/95; Antineoplastic drugs; Apoptosis; Artificial intelligence; Autophagy; Biochemistry; Biomedical and Life Sciences; Biomedicine; Calcium homeostasis; Calcium metabolism; Calcium signalling; Cancer; Cancer therapies; Drug delivery; Drug development; Drug resistance; Endoplasmic reticulum; Homeostasis; Immunosuppressive agents; Intracellular; Intracellular signalling; Lipid metabolism; Medical Biochemistry; Medicine; Metabolism; Mitochondria; Molecular Medicine; Organelles; Oxidative stress; Physiology; Protein folding; Proteins; QD415-436; R; Review Article; Stem Cells; Therapeutic targets; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01137-3

Dynamic interactions between organelles are responsible for a variety of intercellular functions, and the endoplasmic reticulum (ER)–mitochondrial axis is recognized as a representative interorganelle system. Several studies have confirmed that most proteins in the physically tethered sites between the ER and mitochondria, called mitochondria-associated ER membranes (MAMs), are vital for intracellular physiology. MAM proteins are involved in the regulation of calcium homeostasis, lipid metabolism, and mitochondrial dynamics and are associated with processes related to intracellular stress conditions, such as oxidative stress and unfolded protein responses. Accumulating evidence has shown that, owing to their extensive involvement in cellular homeostasis, alterations in the ER–mitochondrial axis are one of the etiological factors of tumors. An in-depth understanding of MAM proteins and their impact on cell physiology, particularly in cancers, may help elucidate their potential as diagnostic and therapeutic targets for cancers. For example, the modulation of MAM proteins is utilized not only to target diverse intracellular signaling pathways within cancer cells but also to increase the sensitivity of cancer cells to anticancer reagents and regulate immune cell activities. Therefore, the current review summarizes and discusses recent advances in research on the functional roles of MAM proteins and their characteristics in cancers from a diagnostic perspective. Additionally, this review provides insights into diverse therapeutic strategies that target MAM proteins in various cancer types. MAM proteins: the hidden players in cancer diagnostics and therapy Understanding the cooperation between organelles, especially the endoplasmic reticulum and mitochondria (the energy factories of cells), is vital to uncover how cellular functions are controlled. However, the exact function of the membranes linking these organelles, termed mitochondria-associated ER membranes (MAMs), in diseases like cancer is still uncertain. In this research, scientists found MAMs to play a vital role in cancer cell function and metabolism by regulating calcium signaling, lipid metabolism, autophagy, and mitochondrial fission. They discovered that changes in MAM proteins can result in inhibition of apoptosis and increased resistance to anticancer drugs. Therefore, therapies targeting MAMs may provide a new method for cancer treatment. The researchers also propose that MAM proteins could be used as diagnostic markers for specific cancers. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.