OPA1-Exon4b Binds to mtDNA D-Loop for Transcriptional and Metabolic Modulation, Independent of Mitochondrial Fusion.
Optic Atrophy 1 (OPA1)
hepatocellular carcinoma
mitochondrial DNA
mitochondrial fusion
mtDNA D-loop
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
12
2019
accepted:
04
03
2020
entrez:
7
5
2020
pubmed:
7
5
2020
medline:
7
5
2020
Statut:
epublish
Résumé
Optic Atrophy 1 (OPA1) has well-established roles in both mitochondrial fusion and apoptotic crista remodeling and is required for the maintenance and distribution of mitochondrial DNA (mtDNA), which are essential for energy metabolism. However, the relationship between OPA1 and mitochondrial metabolism and the underlying mechanisms remain unclear. Here, we show that OPA1-Exon4b modulates mitochondrial respiration and rescues inner mitochondrial membrane potential (Δψm), independent of mitochondrial fusion. OPA1-Exon4b is required for the maintenance of normal TFAM distribution and enhances mtDNA transcription by binding the D-loop of mtDNA. Finally, we show that mRNA levels of OPA1 isoforms containing Exon4b are specifically downregulated in hepatocellular carcinoma (HCC), leading to a reduction in Δψm. Thus, our study demonstrates a novel mitochondrial functional self-recovery pathway involving enhanced mtDNA transcription-mediated recovery of mitochondrial respiratory chain proteins. This mitochondrial fusion-independent pathway may contribute to mitochondrial multi-functional switches in tumorigenesis.
Identifiants
pubmed: 32373606
doi: 10.3389/fcell.2020.00180
pmc: PMC7179665
doi:
Types de publication
Journal Article
Langues
eng
Pagination
180Informations de copyright
Copyright © 2020 Yang, Tang, Lin, Wu, Zeng, Pan, Li, Xiang, Lin, Zhuang, Song, Jiang and Liu.
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