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

Kun Gao; Xiayun Xu; Chenji Wang

doi:10.1016/j.molmed.2023.11.017

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

Trends Mol Med. 2024 Feb;30(2):113-116. doi: 10.1016/j.molmed.2023.11.017. Epub 2023 Dec 19.

Authors

Kun Gao¹, Xiayun Xu², Chenji Wang³

Affiliations

¹ Department of Clinical Laboratory, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: kungao@tongji.edu.cn.
² State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, China.
³ State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: chenjiwang@fudan.edu.cn.

PMID: 38123379
DOI: 10.1016/j.molmed.2023.11.017

Abstract

Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is an autosomal recessive disorder arising from biallelic F-box and leucine-rich repeat (LRR) protein 4 (FBXL4) gene mutations. Recent advances have shown that excessive BCL2 interacting protein 3 (BNIP3)/ BCL2 interacting protein 3 like (BNIP3L)-dependent mitophagy underlies the molecular pathogenesis of MTDPS13. Here, we provide an overview of these groundbreaking findings and discuss potential therapeutic strategies for this fatal disease.

Keywords: BNIP3/BNIP3L; FBXL4; MTDPS13; mitochondria; mitophagy; ubiquitination.

MeSH terms

DNA, Mitochondrial / genetics
Humans
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mitochondria / metabolism
Mitochondrial Encephalomyopathies* / genetics
Mitochondrial Encephalomyopathies* / metabolism
Mitochondrial Encephalomyopathies* / pathology
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Mitophagy* / genetics
Mutation
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism

Substances

DNA, Mitochondrial
Proto-Oncogene Proteins c-bcl-2
Mitochondrial Proteins
BNIP3 protein, human
Membrane Proteins
Proto-Oncogene Proteins
BNIP3L protein, human
Tumor Suppressor Proteins