Asset Details
Do you wish to reserve the book?
TFAM promotes mitochondrial division by increasing mitochondrial Sirt3
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
TFAM promotes mitochondrial division by increasing mitochondrial Sirt3
Do you wish to request the book?
TFAM promotes mitochondrial division by increasing mitochondrial Sirt3
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
TFAM promotes mitochondrial division by increasing mitochondrial Sirt3
2026
Overview
Mitochondrial transcription factor A (TFAM) plays a crucial role in mitochondrial fission beyond its canonical function in mtDNA maintenance. However, how TFAM regulates mitochondrial fission remains only partially understood. Fluorescence microscopy and TEM analyses showed that TFAM knockdown inhibited mitochondrial fission, whereas TFAM overexpression promoted mitochondrial fragmentation, and this mitochondrial morphology phenotype was supported by TEM-based ultrastructural observations in zebrafish embryos with
tfam
disruption. Depletion of Drp1 and MFF in TFAM-overexpressing cells led to elongated mitochondria, indicating that TFAM promotes Drp1- and MFF-dependent mitochondrial fission, which was further supported by the inhibitory effects of Mdivi-1 (Drp1 inhibitor) and Compound C (AMPK inhibitor) on TFAM-induced mitochondrial fission. Western blot and immunofluorescence analyses revealed that TFAM overexpression enhanced the mitochondrial localization and Sirt3-dependent mitochondrial protein deacetylation of Sirtuin 3 (Sirt3), increased phosphorylation of AMPK and MFF, and promoted mitochondrial recruitment of phosphorylated Drp1. Proteinase K protection and cycloheximide chase assays further supported intramitochondrial localization of Sirt3 and increased stability of mitochondrial Sirt3 upon TFAM overexpression. FRET imaging and co-immunoprecipitation demonstrated a direct TFAM-Sirt3 interaction mediated by TFAM’s HMG-box A domain. Targeted mutagenesis or deletion of the HMG-box A domain disrupted the TFAM-Sirt3 interaction, impaired Sirt3 mitochondrial localization and Sirt3-dependent mitochondrial protein deacetylation, and abolished TFAM-mediated mitochondrial fission. Analysis of TCGA data showed that high TFAM-SIRT3 co-expression is associated with overall survival across cancers, particularly in Kidney Renal Clear Cell Carcinoma (KIRC), where TFAM is downregulated (whereas SIRT3 is not). Together, these findings demonstrate that TFAM promotes mitochondrial fission via direct interaction with Sirt3, thereby activating the AMPK/MFF/Drp1 pathway.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/109
/ 13/95
/ 14
/ 14/63
/ 82/1
/ 82/80
/ 96/34
/ 96/35
/ AMP-Activated Protein Kinases - metabolism
/ Animals
/ Biomedical and Life Sciences
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Embryos
/ Humans
/ Kinases
/ Mitochondria - ultrastructure
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Plasmids
/ Proteins
/ Transcription Factors - genetics
