Review
Open Access
Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review)
- Authors:
- Yi Liu
- Xianda Che
- Wei Wei
- Chong Teng
- Huimin Li
-
View Affiliations / Copyright
Affiliations:
Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang 322000, P.R. China, Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Orthopedics, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang 322000, P.R. China, Department of Orthopedics, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang 322000, P.R. China
-
Article Number:
227
|
Published online on:
June 22, 2026
https://doi.org/10.3892/ijmm.2026.5898
- Expand metrics +
Metrics:
Total
Views: 0
(Spandidos Publications: | PMC Statistics:
)
Metrics:
Total PDF Downloads: 0
(Spandidos Publications: | PMC Statistics:
)
This article is mentioned in:
Abstract
Mitochondria‑endoplasmic reticulum contact sites (MERCs) are dynamic, nanoscale membrane domains that serve as crucial signaling hubs for inter‑organellar communication. These specialized interfaces are maintained by a complex network composed of tethering, promoter, and disruptor proteins and coordinate a wide range of cellular processes, such as calcium and zinc ion homeostasis, lipid biosynthesis and transfer, redox signaling, mitochondrial dynamics (fission, fusion and mitophagy), autophagy, apoptosis, inflammation and cellular senescence. Accordingly, the structural and functional integrity of MERCs is vital for cellular adaptation and survival. Nevertheless, MERC plasticity is often impaired in various human pathologies. Alterations in MERC composition, abundance, or function are regarded as pathogenic mechanisms in neurodegenerative diseases, metabolic disorders, cardiovascular conditions, cancer and orthopedic diseases. Common manifestations of MERC dysfunction include disrupted ion signaling, bioenergetic failure, excessive oxidative stress, and impaired organelle quality control. Therefore, targeted modulation of MERCs represents a promising therapeutic avenue. However, translating this potential into clinical practice faces considerable challenges. This is because MERC function is dynamic, context‑dependent and dualistic; both excessive and deficient coupling can drive pathology. Future progress hinges on deciphering the precise regulatory codes that govern MERC assembly, developing tools for real‑time, high‑resolution in vivo analysis, and designing innovative, cell‑type‑specific interventions that normalize rather than simply inhibit or enhance MERC function. A multidisciplinary approach integrating spatial proteomics, super‑resolution imaging, and advanced disease modeling is warranted for unlocking the full diagnostic and therapeutic potential of these organelle contact sites.
