Patitucci 2023 bioRxiv
| Patitucci C, Hernández-Camacho JD, Vimont E, Cokelaer T, Chaze T, Gianetto QG, Matondo M, Gazi A, Nemazanyy I, Stroud DA, Hock DH, Donnarumma E, Wai T (2023) Mtfp1 ablation enhances mitochondrial respiration and protects against hepatic steatosis. bioRxiv https://doi.org/10.1101/2023.04.26.538374 . |
» bioRxiv. Open Access
Patitucci Cecilia, Hernandez-Camacho Juan Diego, Vimont Elodie, Cokelaer Thomas, Chaze Thibault, Gianetto Quentin Giai, Matondo Mariette, Gazi Anastasia, Nemazanyy Ivan, Stroud David A, Hock Daniella H, Donnarumma Erminia, Wai Timothy (2023) bioRxiv
Abstract: Hepatic steatosis is the result of an imbalance between nutrient delivery and metabolism in the liver. It is the first hallmark of Non-alcoholic fatty liver disease (NAFLD) and is characterized by the accumulation of excess lipids in the liver that can drive liver failure, inflammation, and cancer. Mitochondria control the fate and function of cells and compelling evidence implicates these multifunctional organelles in the appearance and progression of liver dysfunction, although it remains to be elucidated which specific mitochondrial functions are actually causally linked to NAFLD. Here, we identified Mitochondrial Fission Process 1 protein (MTFP1) as a key regulator of mitochondrial and metabolic activity in the liver. Deletion of Mtfp1 in hepatocytes is physiologically benign in mice yet leads to the upregulation of oxidative phosphorylation (OXPHOS) activity and mitochondrial respiration, independently of mitochondrial biogenesis. Consequently, hepatocyte-specific knockout mice are protected against high fat diet-induced hepatic steatosis and metabolic dysregulation. Additionally, we find that deletion of Mtfp1 in liver mitochondria inhibits mitochondrial permeability transition pore opening in hepatocytes, conferring protection against apoptotic liver damage in vivo and ex vivo. Our work uncovers novel functions of MTFP1 in the liver, positioning this gene as an unexpected regulator of OXPHOS and a therapeutic candidate for NAFLD.
• Bioblast editor: Plangger M • O2k-Network Lab: FR Paris Wai T
Labels: MiParea: Respiration
HRR: Oxygraph-2k
2023-06
