Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics
- Author(s)
- Wei, Shibo; Shin, Soyeon; Ryu, Dongryeol; Oh, Chang-Myung
- Type
- Article
- Citation
- Diabetes and Metabolism Journal, v.50, no.5, pp.825 - 843
- Issued Date
- 2026-09
- Abstract
- Sarcopenia in type 2 diabetes mellitus is increasingly recognized as a mechanistic consequence of chronic metabolic stress rather than mere age-related comorbidity. This review synthesizes evidence demonstrating how insulin resistance, hyperglycemia, lipotoxicity, and inflammation converge on skeletal muscle mitochondrial proteostasis to drive progressive decline. We evaluate seven pathway modules—mitochondrial dynamics, mitophagy, biogenesis, oxidative phosphorylation, nicotinamide adenine dinucleotide (NAD+)/sirtuin (SIRT)-linked regulation, protein import, and the mitochondrial unfolded protein response (UPRmt)—across an evidence map encompassing basic, clinical, and multi-omics studies. Dynamics and mitophagy represent mechanistically central quality-control nodes; their impairment permits dysfunctional organelle accumulation and promotes atrophic cascades. Direct evidence density, however, remains weighted toward oxidative phosphorylation and mitochondrial biogenesis. NAD+/SIRT-linked regulation, protein import fidelity, and UPRmt represent mechanistically upstream but comparatively underinvestigated signals. We propose a diabetes-centered framework where mitochondrial proteostasis failure mediates atrophy and reinforces insulin resistance via a self-amplifying feed-forward loop, supported by pathway responsiveness to coherent interventions. Human multi-omics data highlight network-level dysregulation rather than isolated defects, underscoring module-based biomarker strategies. Translationally, exercise remains the mechanistic cornerstone, while pathway-directed adjuncts—NAD+ precursor repletion, mitophagy modulators, and emerging pharmacotherapeutics—are warranted for patients with identifiable module-specific failure patterns.
- Publisher
- 대한당뇨병학회
- ISSN
- 2233-6079
- DOI
- 10.4093/dmj.2026.0310
- URI
- https://scholar.gist.ac.kr/handle/local/34637
- 공개 및 라이선스
-
- 파일 목록
-
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.