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FUNDC1-dependent mitophagy determines axon regeneration capacity.
Wenlei Li1, Yujiao Liu1, Ruixuan Liu2
1State Key Laboratory of Medicinal Chemical Biology and Frontier of Science Center for Cell Response, College of Life Sciences, Nankai University, Tianjin, China.
Autophagy
|March 8, 2026
Summary
FUNDC1-mediated mitophagy is crucial for nerve regeneration by clearing damaged mitochondria. This process enhances axonal regrowth and peripheral nerve recovery through improved mitochondrial quality and carnosine biosynthesis.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Biology
Background:
- Axon regeneration after nerve injury is essential for functional recovery.
- Mitochondrial dysfunction can impede neuronal repair.
- Mitophagy, the selective degradation of mitochondria, is a key cellular quality control process.
Purpose of the Study:
- To investigate the role of FUN14 domain containing 1 (FUNDC1)-mediated mitophagy in neuronal axon regeneration.
- To elucidate the molecular mechanisms by which FUNDC1 influences nerve repair.
- To explore therapeutic strategies targeting mitophagy for enhanced peripheral nerve recovery.
Main Methods:
- Overexpression and knockout of FUNDC1 in neuronal models.
- In vitro and in vivo studies of axonal regeneration after nerve injury.
- Metabolic profiling and molecular analysis of signaling pathways.
- Treatment with mitophagy inducers like urolithin A.
Main Results:
- FUNDC1 overexpression significantly enhanced axonal regeneration in vitro and in vivo.
- FUNDC1-mediated mitophagy maintained mitochondrial health and promoted axon regrowth.
- Mice lacking FUNDC1 showed impaired nerve regeneration, which was rescued by WT FUNDC1.
- Metabolic analysis revealed enhanced carnosine biosynthesis driven by FUNDC1-mediated mitophagy, contributing to nerve recovery.
Conclusions:
- FUNDC1-mediated mitophagy is a critical determinant of intrinsic neuronal regenerative capacity.
- Targeting FUNDC1 and mitophagy offers a promising therapeutic avenue for peripheral nerve injury.
- The study links mitochondrial quality control, metabolic adaptation, and nerve regeneration via FUNDC1.

