Healthy mitochondria attenuate metabolic dysfunction-associated steatohepatitis by restoring cell metabolism
Year: 2025
Type: article
Abstract: Metabolic dysfunction-associated steatohepatitis (MASH) has become a major global health issue. Mitochondrial damage plays a crucial role in the development and progression of MASH. Therefore, it is speculated that mitochondrial transplantation therapy, which could replace dysfunctional mitochondria with normal ones, might potentially restore the liver cell metabolism of MASH. In palmitate-damaged AML-12 hepatocytes, exogenous mitochondria could eliminate lipid deposits and recover cell viability. However, in transforming growth factor β (TGF-β)-activated hepatic stellate cells (HSCs), the exogenous mitochondria showed the capability to inhibit the generation of α-smooth muscle actin (α-SMA) and collagen I. Moreover, the mechanism by which the exogenous mitochondria initiated the mitochondria-nucleus signaling pathway of liver cells was studied. The results showed the mitochondria could prevent metabolism disorders in the liver cells by regulating silent information regulator 1 (SIRT1) activity. Subsequently, a MASH animal model was established by the administration of a high-fat diet and the intraperitoneal injection of carbon tetrachloride to Kunming mice. The results indicated that the mitochondrial therapy significantly inhibited the livery injury and restored liver cell function in the experimental MASH mice (p < 0.01). The mitochondrial therapy would be a promising strategy to improve MASH pathological features, which could be developed as a new treatment option against MASH.
Source: Molecular Biomedicine
Authors: Peiyu Zhou, Jingli Li, Yafang Xie, Xiaorong Li, Zhihong Cui, Ailing Fu
Institution: Southwest University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
OpenAlex ID: W4415075136