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FBXL4 mutation-caused mitochondrial DNA depletion syndrome is driven by BNIP3/BNIP3L-dependent excessive mitophagy

Kun Gao1, Xiayun Xu2, Chenji Wang2

  • 1Department of Clinical Laboratory, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

Trends in Molecular Medicine
|December 20, 2023
PubMed

Insights

Mitochondrial DNA depletion syndrome 13 (MTDPS13), caused by FBXL4 gene mutations, results from excessive mitophagy. This overview discusses findings and potential therapies for this fatal genetic disorder.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is a severe autosomal recessive disorder.
  • It is caused by mutations in the F-box and leucine-rich repeat (LRR) protein 4 (FBXL4) gene.

Purpose of the Study:

  • To provide an overview of recent findings on the molecular pathogenesis of MTDPS13.
  • To discuss potential therapeutic strategies for MTDPS13.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of molecular mechanisms underlying MTDPS13 pathogenesis.

Main Results:

  • Excessive mitophagy, dependent on BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L), is identified as the core molecular mechanism.
  • FBXL4 gene mutations lead to this pathological mitophagy process.

Conclusions:

  • Understanding the role of excessive mitophagy in MTDPS13 opens avenues for targeted therapies.
  • Further research into BNIP3/BNIP3L-dependent mitophagy may yield treatments for this fatal disease.
Keywords:
BNIP3/BNIP3LFBXL4MTDPS13mitochondriamitophagyubiquitination

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