TUFM: a central regulator in mitochondrial quality control and beyond

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Tu translation elongation factor, mitochondrial (TUFM) is a nuclear-encoded GTPase essential for mitochondrial protein synthesis.
• TUFM also acts as a key regulator of mitochondrial quality control (MQC), influencing biogenesis, dynamics, and mitophagy.
• Post-translational modifications precisely control TUFM's localization and function in cellular homeostasis and stress responses.

Purpose of the Study:

• To review current mechanistic insights into TUFM's role as a central MQC coordinator.
• To delineate how TUFM imbalance affects cellular trajectories toward survival or death.
• To explore therapeutic strategies targeting the TUFM-MQC axis for disease treatment.

Main Methods:

• Literature review synthesizing current research on TUFM.
• Analysis of TUFM's regulatory mechanisms, including post-translational modifications.
• Exploration of TUFM's involvement in host-pathogen interactions and disease pathology.

Main Results:

• TUFM's function is dictated by its subcellular localization and is modulated by various post-translational modifications.
• Viruses can exploit TUFM's pro-mitophagic function to evade host antiviral defenses.
• TUFM hyperactivation promotes oncogenesis, while deficiency contributes to neurodegeneration and metabolic dysfunction.

Conclusions:

• The TUFM-MQC axis acts as a cellular fate switch, with dysregulation leading to diverse pathological outcomes.
• Understanding TUFM's regulatory logic and spatiotemporal dynamics is crucial for developing targeted therapies.
• Targeting TUFM offers promising avenues for restoring cellular homeostasis in various diseases.