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Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review)

  • Authors:
    • Yue Liu
    • Xuejia Gong
    • Shasha Xing
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    Affiliations: GCP Institution, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 275
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    Published online on: July 29, 2025
       https://doi.org/10.3892/mmr.2025.13640
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Abstract

Cardiovascular disease (CVD), which includes conditions such as coronary heart disease, hypertension, heart failure and diabetes cardiomyopathy, is a major cause of mortality among middle‑aged and elderly populations worldwide; however, there is a concerning trend of individuals of increasingly younger ages being affected. Despite extensive research and numerous treatments available, CVD remains a major health threat for middle‑aged and elderly individuals due to its complex causes and the effect of environmental and lifestyle factors. In recent years, the structural and functional abnormalities of mitochondria and endoplasmic reticulum (ER) organelles have been associated with CVD. In addition to the intrinsic role of organelles, the interaction between organelles, particularly the homeostasis imbalance between the mitochondria and the ER through the interaction of the mitochondria‑associated ER membrane (MAM), serves a key role in CVD, such as ischemia‑reperfusion, diabetic cardiomyopathy and heart failure. The main mechanism involves regulating lipid transport, calcium homeostasis, mitochondrial function, cell survival and death, as well as signal transduction. The present review summarized recent advancements in MAM research, elucidated key mechanisms that influence MAM homeostasis, highlighted its significance in cardiovascular health and disease and explored its potential as a therapeutic target for CVD, thereby providing a theoretical foundation for future research.
View Figures

Figure 1

Representation of proteins and
protein complexes involved in the crosstalk between the ER and
mitochondria in MAMs. There are mainly six protein/protein
complexes located in MAMs, including IP3R1-VDAC1-Grp75,
VAPB-PTPIP51, Mfn2, PACS-2, Sig-1R, Rab32 and MICOS. ER,
endoplasmic reticulum; MAM, mitochondria-associated ER membrane;
IP3R1, inositol 1,4,5-triphosphate receptor type 1; VDAC1,
voltage-dependent anion channel-1; Grp75, glucose-regulated protein
75; VAPB, vesicle-associated membrane protein-associated protein B;
PTPIP51, protein tyrosine phosphatase interacting protein 51; Mfn2,
mitofusin 2; PACS-2, phosphofurin acidic cluster sorting protein 2;
Sig-1R, σ-1 receptor; MICOS, mitochondrial contact site and cristae
organizing system; Sam, sorting and assembly machinery.

Figure 2

Effect of MAMs homeostasis imbalance
on CVD. The association between the signaling pathways of MAMs
homeostasis imbalance and different types of cardiovascular
diseases, including myocardial hypertrophy, coronary heart disease
and diabetic cardiomyopathy. MAM, mitochondria-associated
endoplasmic reticulum membrane; CVD, cardiovascular disease; ER,
endoplasmic reticulum; PACS-2, phosphofurin acidic cluster sorting
protein 2; IP3R2, inositol 1,4,5-trisphosphate receptor type 2;
FUNDC1, FUN14 domain containing 1; VDAC1, voltage-dependent anion
channel 1; DRP1, dynamin-related protein 1; Rab9, Ras-related
protein Rab-9A; Fis1, fission 1 protein; Mfn2, mitofusin 2;
TMEM215, transmembrane protein 215; Opa1, optic atrophy 1; DIAPH1,
Diaphanous-1.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Gong X and Xing S: Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review). Mol Med Rep 32: 275, 2025.
APA
Liu, Y., Gong, X., & Xing, S. (2025). Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review). Molecular Medicine Reports, 32, 275. https://doi.org/10.3892/mmr.2025.13640
MLA
Liu, Y., Gong, X., Xing, S."Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review)". Molecular Medicine Reports 32.4 (2025): 275.
Chicago
Liu, Y., Gong, X., Xing, S."Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review)". Molecular Medicine Reports 32, no. 4 (2025): 275. https://doi.org/10.3892/mmr.2025.13640
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Gong X and Xing S: Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review). Mol Med Rep 32: 275, 2025.
APA
Liu, Y., Gong, X., & Xing, S. (2025). Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review). Molecular Medicine Reports, 32, 275. https://doi.org/10.3892/mmr.2025.13640
MLA
Liu, Y., Gong, X., Xing, S."Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review)". Molecular Medicine Reports 32.4 (2025): 275.
Chicago
Liu, Y., Gong, X., Xing, S."Mitochondrial‑endoplasmic reticulum crosstalk: Molecular mechanisms and implications for cardiovascular disease (Review)". Molecular Medicine Reports 32, no. 4 (2025): 275. https://doi.org/10.3892/mmr.2025.13640
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