Organelle stress and alterations in interorganelle crosstalk during liver fibrosis

Abstract

The synchronous functioning and quality control of organelles ensure cell survival and function and are essential for maintaining homeostasis. Prolonged exposure to stressors (viruses, bacteria, parasitic infections, alcohol, drugs) or genetic mutations often disrupt the functional integrity of organelles which plays a critical role in the initiation and progression of several diseases including chronic liver diseases. One of the most important pathologic consequences of chronic liver diseases is liver fibrosis, characterized by tissue scarring due to the progressive accumulation of extracellular matrix components. Left untreated, fibrosis may advance to lifethreatening complications such as cirrhosis, hepatic decompensation, and HCC, which collectively accounts for ∼1 million deaths per year worldwide.Owing to the lack of treatment options that can regress or reverse cirrhosis, liver transplantation is currently the only available treatment for end-stage liver disease. However, the limited supply of usable donor organs, adverse effects of lifelong immunosuppressive regimes, and financial considerations pose major challenges and limit its application. Hence, effective therapeutic strategies are urgently needed. An improved understanding of the organellelevel regulation of fibrosis can help devise effective antifibrotic therapies focused on reducing organelle stress, limiting organelle damage, improving interorganelle crosstalk, and restoring organelle homeostasis; and could be a potential clinical option to avoid transplantation. This review provides a timely update on the recent findings and mechanisms covering organelle-

Dual-Targeting Macrophages and Hepatic Stellate Cells by Modified Albumin Nanoparticles for Liver Cirrhosis Treatment

“…Liver disease is a major global health issue, with 2 million deaths occurring each year, accounting for 4% of all global deaths. As the end stage of chronic liver disease, cirrhosis and its complications contribute to more than half of this mortality, causing significant clinical and economic burden around the world. − In clinical practice, there is currently no effective treatment available for liver cirrhosis except for liver transplantation. , Therefore, there is a strong need for curative interventions in the cirrhosis process (Scheme ).…”

“…1−3 In clinical practice, there is currently no effective treatment available for liver cirrhosis except for liver transplantation. 4,5 Therefore, there is a strong need for curative interventions in the cirrhosis process (Scheme 1).…”

Glaucocalyxin A attenuates carbon tetrachloride‐induced liver fibrosis and improves the associated gut microbiota imbalance

“…Liver fibrosis refers to the pathophysiological process of dysplasia on the connective tissue of the liver, caused by a variety of pathogenic factors. It is also a response to wound healing that is caused by the damage to the liver as a resultant effect of most chronic liver diseases (Sinha et al, 2023). Persistent deterioration of the liver gradually progresses to cirrhosis, possibly increasing the possibility of liver cancer and ultimate failure (Shan et al, 2019).…”

Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy

“…The dysfunction of LSECs also promotes inflammatory pathways and steatosis [ 14 ]. Compromised hepatocyte integrity and activation of inflammatory pathways—such as c-Jun N-terminal kinase-1 (JNK1) and the nuclear factor kappa B (NFκB) signaling pathways—with suppression of peroxisome proliferator-activated receptor-α (PPAR-α) could induce trans-differentiation of quiescent HSCs into myofibroblast-like activated HSCs (aHSCs) [ 15 , 16 ]. Upon activation, the HSCs lose the storage of vitamin A and become proliferative.…”