Authors
Jingwen Liu, Kewei Li, Ying Deng, Xi Li, Ruhan Yang, Ping Huang, Chunyan Li, Yueshui Zhao, Fukuan Du, Yu Chen, Jing Shen, Zhangang Xiao, Kangxing Zhu, Tao Shui, Jianqiao Zhong, Mingxing Li, Xu Wu
Published in
Pharmacological research. Pages 108410. Aug 21, 2026. Epub Aug 21, 2026.
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to liver mitochondrial dysfunction, which is driven not as an isolated event but by a self-amplifying injury loop involving impaired intrinsic quality control, aberrant organelle crosstalk, and dysregulated gut-liver signaling. This review summarizes findings in three interconnected regulatory layers: (1) intrinsic mitochondrial quality control (MQC) (PINK1/Parkin- and BNIP3/NIX-mediated mitophagy, Drp1/Mfn-driven dynamics, and chaperone/protease-maintained proteostasis); (2) organelle interactions (ER-mitochondria contacts, lipid droplet tethering, and lysosome crosstalk); and (3) extrinsic modulation via the gut-derived metabolites. We highlight that dysregulated mitophagy and mitochondrial fragmentation promote lipid accumulation and inflammation, whereas the abnormal formation of mitochondria-associated membranes (MAMs) exacerbates calcium overload and oxidative stress. Furthermore, short-chain fatty acids and bile acids derived from the gut differentially modulate mitochondrial bioenergetics. Preclinical evidence indicates that restoring MQC or targeting organelle interactions can improve MASLD symptoms. Given the multifactorial nature of MASLD, single-target interventions are insufficient; multi-target strategies and tissue-specific delivery are essential for clinical translation.
PMID:
42628854
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.
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