Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.
10.1016/j.apsb.2025.04.019
- Author:
Zihan WANG
1
;
Kaige ZHANG
1
;
Minghao HUANG
1
;
Dehao SHANG
1
;
Xiaomin HE
1
;
Zhou WU
2
;
Xu YAN
3
;
Xinwen ZHANG
1
Author Information
1. Department of Oral Implantology, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China.
2. Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
3. The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110002, China.
- Publication Type:Review
- Keywords:
Alzheimer's disease;
CHCHD10;
CHCHD2;
Cristae junctions;
MIC10;
MIC60;
MICOS complex;
Mitochondria
- From:
Acta Pharmaceutica Sinica B
2025;15(6):2966-2984
- CountryChina
- Language:English
-
Abstract:
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.
