HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120 acetylation

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• p53 acetylation is crucial for its pro-apoptotic functions.
• The precise regulatory mechanisms and physiological roles of p53 acetylation remain incompletely understood.

Purpose of the Study:

• To investigate the role of Histone deacetylase 6 (HDAC6) in regulating p53 acetylation at lysine 120 (K120) within mesenchymal stem cells (MSCs).
• To elucidate the impact of HDAC6 on apoptosis and mitochondrial function in MSCs.

Main Methods:

• Assessed p53 K120 acetylation levels in MSCs with varying HDAC6 expression.
• Utilized wild-type and catalytically dead HDAC6 for rescue experiments.
• Analyzed apoptosis through caspase-dependent pathways and evaluated mitochondrial function, including reactive oxygen species (ROS) production and oxidative phosphorylation.

Main Results:

• HDAC6 negatively regulates pro-apoptotic p53 acetylation at K120 in MSCs.
• Loss of HDAC6 increases p53 K120 acetylation, leading to caspase-dependent apoptosis via Bax transactivation and Bcl-2 suppression.
• HDAC6 deficiency impairs mitochondrial function, evidenced by aberrant ROS production and defective oxidative phosphorylation.

Conclusions:

• HDAC6 is a key regulator of p53 K120 acetylation and mitochondrial homeostasis in MSCs.
• Targeting HDAC6 activity presents a potential strategy for improving MSC-based therapeutic applications.