Hedgehog/GLI Signaling at the Interface of Sterol Metabolism, Mitochondrial ROS Signaling and Cellular Plasticity

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Hedgehog (Hh)/GLI signaling is traditionally known for its role in development.
• Emerging evidence highlights its involvement in cellular metabolism and stress adaptation.
• Mitochondria are key regulators of reactive oxygen species (ROS), crucial for cellular signaling.

Purpose of the Study:

• To review the role of Hh/GLI signaling in mitochondrial function and redox homeostasis.
• To explore the interplay between Hh/GLI signaling, ROS production, and metabolic adaptation.
• To discuss the integration of sterol metabolism and antioxidant pathways within this regulatory network.

Main Methods:

• Literature review of studies investigating Hh/GLI signaling, mitochondrial function, and redox homeostasis.
• Analysis of mechanisms by which ROS production influences Hh/GLI activity.
• Examination of the connection between sterol metabolism, lipid metabolism, and mitochondrial regulation.

Main Results:

• Hh/GLI signaling influences and is influenced by ROS production, with GLI activity modulated by redox-dependent mechanisms.
• The pathway is linked to mitochondrial bioenergetics, dynamics, and quality control.
• Cholesterol and oxysterols modulate Smoothened activation, connecting lipid metabolism to mitochondrial and redox balance.

Conclusions:

• Hh/GLI signaling plays a significant role in mitochondrial redox adaptation by integrating metabolic and oxidative signals.
• This pathway contributes to cellular adaptation in both physiological and pathological conditions.
• Understanding these interactions is crucial for comprehending tissue responses to various stimuli like irradiation, inflammation, and aging.