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Updated: Aug 23, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Mitochondrial-centric regulatory networks in MASLD: Integrating quality control, organelle interactions, and
Jingwen Liu1, Kewei Li2, Ying Deng3
1Cell Therapy & Cell Drugs Key Laboratory of Luzhou, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
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. It is highlighted 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, bile acids and other metabolites 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.
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