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T-cell-restricted intracellular antigen 1 facilitates mitochondrial fragmentation by enhancing the expression of mitochondrial fission factor
- Source :
- Cell Death & Differentiation. 24:49-58
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Mitochondrial morphology is dynamically regulated by the formation of small fragmented units or interconnected mitochondrial networks, and this dynamic morphological change is a pivotal process in normal mitochondrial function. In the present study, we identified a novel regulator responsible for the regulation of mitochondrial dynamics. An assay using CHANG liver cells stably expressing mitochondrial-targeted yellow fluorescent protein (mtYFP) and a group of siRNAs revealed that T-cell intracellular antigen protein-1 (TIA-1) affects mitochondrial morphology by enhancing mitochondrial fission. The function of TIA-1 in mitochondrial dynamics was investigated through various biological approaches and expression analysis in human specimen. Downregulation of TIA-1-enhanced mitochondrial elongation, whereas ectopic expression of TIA-1 resulted in mitochondria fragmentation. In addition, TIA-1 increased mitochondrial activity, including the rate of ATP synthesis and oxygen consumption. Further, we identified mitochondrial fission factor (MFF) as a direct target of TIA-1, and showed that TIA-1 promotes mitochondrial fragmentation by enhancing MFF translation. TIA-1 null cells had a decreased level of MFF and less mitochondrial Drp1, a critical factor for mitochondrial fragmentation, thereby enhancing mitochondrial elongation. Taken together, our results indicate that TIA-1 is a novel factor that facilitates mitochondrial dynamics by enhancing MFF expression and contributes to mitochondrial dysfunction.
- Subjects :
- Dynamins
0301 basic medicine
Mitochondrial fission factor
Mitochondrion
Biology
Mitochondrial apoptosis-induced channel
Cell Line
GTP Phosphohydrolases
Mitochondrial Proteins
Mice
03 medical and health sciences
Adenosine Triphosphate
Oxygen Consumption
Bacterial Proteins
parasitic diseases
Animals
Humans
RNA, Messenger
cardiovascular diseases
RNA, Small Interfering
Fragmentation (cell biology)
3' Untranslated Regions
Molecular Biology
Original Paper
ATP synthase
Membrane Proteins
Cell Biology
Mitochondria
T-Cell Intracellular Antigen-1
nervous system diseases
Cell biology
Luminescent Proteins
MicroRNAs
030104 developmental biology
Microscopy, Fluorescence
DNAJA3
biology.protein
Apoptosis-inducing factor
RNA Interference
Mitochondrial fission
Microtubule-Associated Proteins
Plasmids
Subjects
Details
- ISSN :
- 14765403 and 13509047
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Cell Death & Differentiation
- Accession number :
- edsair.doi.dedup.....fed83e5eb6fd5121648ef9cf1cd3e02f