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. 2025 Mar 28;30(1):35.
doi: 10.1186/s11658-025-00714-w.

MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review

A Anjana Mohan  1 , Priti Talwar  2
Affiliations

MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review

A Anjana Mohan et al. Cell Mol Biol Lett. .

Abstract

Mitochondria-associated membranes (MAMs) are tethering regions amid the membranes of the endoplasmic reticulum (ER) and mitochondria. They are a lipid raft-like structure occupied by various proteins that facilitates signal transduction between the two organelles. The MAM proteome participates in cellular functions such as calcium (Ca2+) homeostasis, lipid synthesis, ER stress, inflammation, autophagy, mitophagy, and apoptosis. The human kinome is a superfamily of homologous proteins consisting of 538 kinases. MAM-associated kinases participate in the aforementioned cellular functions and act as cell fate executors. Studies have proved the dysregulated kinase interactions in MAM as an etiology for various diseases including cancer, diabetes mellitus, neurodegenerative diseases, cardiovascular diseases (CVDs), and obesity. Several small kinase inhibitory molecules have been well explored as promising drug candidates in clinical trials with an accelerating impact in the field of precision medicine. This review narrates the physiological actions, pathophysiology, and therapeutic potential of MAM-associated kinases with recent updates in the field.

Keywords: Cancer; Diabetes; ER stress; Kinases; MAM; Mitophagy; Neurodegenerative disease; Therapeutics.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable as this systematic review does not involve experimental procedures on human participants or animals. Consent of publication: Not applicable as this systematic review does not contain any person’s data in any form. Competing interests: The authors declare no competing interests.

Figures

Fig.1
Fig.1
MAM-associated proteins and functions: MAM is a platform for anchoring various proteins that are crucial for ER–mitochondria (MT) tethering, mitochondrial fragmentation, Ca2+ homeostasis, and apoptosis
Fig. 2
Fig. 2
MAM kinases PKA, PLK, and Akt are involved in Ca2+ flux. PI3K forms a re-autophagosome structure (PAS) along with BECN1 and autophagosome markers. IRE1 is involved in stress responses such as UPR, RIDD, and apoptosis
Fig.3
Fig.3
The MAM kinase PERK branch is one of the three UPR pathways. Mfn2 acts as the upstream regulator of PERK. LRRK detaches from E3 ubiquitin ligases and facilitates their PERK-mediated phosphorylation and subsequent MAM protein degradation. PINK1 actively participates in autophagy and modulates mitochondrial motility. GSK-3 regulates apoptosis, and AMPK regulates MAM contacts and fission according to the energy state of the cell
Fig.4
Fig.4
MAM kinase PDK is involved in Ca2+ transport via the IP3R–Grp75–VDAC1 channel and inhibits acetyl CoA formation from pyruvate. The activity of PDK is regulated by insulin. CK2A1 takes part in Ca2+ transport via PKD2. Ribosome-attached mTORC2 phosphorylates Akt and carries out downstream events
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References

    1. Barazzuol L, Giamogante F, Calì T. Mitochondria associated membranes (MAMs): architecture and physiopathological role. Cell Calcium. 2021. 10.1016/j.ceca.2020.102343. - PubMed
    1. Liu J, Yang J. Mitochondria-associated membranes: a hub for neurodegenerative diseases. Biomed Pharmacother. 2022. 10.1016/j.biopha.2022.112890. - PubMed
    1. Wu H, Carvalho P, Voeltz GK. Here, there and everywhere: the importance of ER membrane contact sites. Science. 2018;361:6401. - PMC - PubMed
    1. Wozny MR, Di Luca A, Morado DR, Picco A, Khaddaj R, Campomanes P, et al. In situ architecture of the ER–mitochondria encounter structure. Nature 2023;618(7963):188–92. - PMC - PubMed
    1. Bernhard W, Rouiller C. Close topographical relationship between mitochondria and ergastoplasm of liver cells in a definite phase of cellular activity. J Biophys Biochem Cytol. 1956;2(4 Suppl):73–8. - PMC - PubMed

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