Journal Article Epublish
PubMed: 40806508 DOI: 10.3390/ijms26157373
Analysis of the Mitochondrial Dynamics in NAFLD: Drp1 as a Marker of Inflammation and Fibrosis.
Int J Mol Sci 26(15)
Authors: Maël Padelli, Jocelyne Hamelin, Christophe Desterke, Mylène Sebagh, Raphael Saffroy, Claudio Garcia Sanchez, Audrey Coilly, Jean-Charles Duclos-Vallée, Didier Samuel, Antoinette Lemoine
Affiliations
- Service de Biochimie et Oncogénétique, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France.
- Faculté de Médecine du Kremlin Bicêtre, Université Paris-Saclay, INSERM UMRS-1310, 94276 Le Kremlin-Bicêtre, France.
- Laboratoire d'Anatomopathologie, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), 94800 Villejuif, France.
- UMR-S 1193, Inserm, Physiopathogénèse et Traitement des Maladies du Foie, 94800 Villejuif, France.
- Centre Hépatobiliaire, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Saclay, 94800 Villejuif, France.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, projected to affect 55% globally by 2040. Up to one-third of NAFLD patients develop non-alcoholic steatohepatitis (NASH), with 40% progressing to fibrosis. However, there are currently few reliable tools to predict disease progression. Impaired mitochondrial dynamics, characterized by dysregulated fission, fusion, and mitophagy, have emerged as key events in NAFLD pathophysiology, contributing to hepatocyte death and inflammation. This study explored the transition from steatosis to NASH through transcriptomic analyses, including data from patients with steatosis and those with NASH at different fibrosis stages. By identifying a transcriptomic signature associated with disease progression, the study revealed increased expression of genes involved in mitochondrial dynamics in NASH compared to steatosis and during NASH-related fibrosis. Histological analyses highlighted the central role of Dynamin-related protein 1 (Drp1), a dynamin GTPase essential for mitochondrial fission and mitophagy. In human liver biopsies, Drp1 expression progressively increased from NAFLD to NASH and NASH-related fibrosis and cirrhosis, predominantly in Kupffer cells. These finding suggest Drp1 is a potential driver of the transition to more severe liver damage, making it a promising biomarker for NASH development and progression and a potential therapeutic target in metabolic disorders.
MeSH
Liver Diseases, Fibrosis, Non-Alcoholic Fatty Liver Disease, Disease Progression, Mitochondrial Dynamics, Liver, Alcoholics, Mitophagy