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T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- Mitochondria undergo frequent morphological changes to control their function. We show here that T-cell intracellular antigens (TIA1b/TIARb) and Hu antigen R (HuR) have antagonistic roles in mitochondrial function by modulating the expression of mitochondrial shaping proteins. Expression of TIA1b/TIARb alters the mitochondrial dynamic network by enhancing fission and clustering, which is accompanied by a decrease in respiration. In contrast, HuR expression promotes fusion and cristae remodeling and increases respiratory activity. Mechanistically, TIA proteins downregulate the expression of optic atrophy 1 (OPA1) protein via switching of the splicing patterns of OPA1 to facilitate the production of OPA1 variant 5 (OPA1v5). Conversely, HuR enhances the expression of OPA1 mRNA isoforms through increasing steady-state levels and targeting translational efficiency at the 3' untranslated region. Knockdown of TIA1/ TIAR or HuR partially reversed the expression profile of OPA1, whereas knockdown of OPA1 or overexpression of OPA1v5 provoked mitochondrial clustering. Middle-term expression of TIA1b/TIARb triggers reactive oxygen species production and mitochondrial DNA damage, which is accompanied by mitophagy, autophagy, and apoptosis. In contrast, HuR expression promotes mitochondrion-dependent cell proliferation. Collectively, these results provide molecular insights into the antagonistic functions of TIA1b/TIARb and HuR in mitochondrial activity dynamics and suggest that their balance might contribute to mitochondrial physiopathology.<br />Spanish Ministry of Economic Affairs and Competitiveness (BFU2011-29653 and BFU2014-57735R) to Jose M. Izquierdo; The CBMSO receives an institutional grant from Fundacion Ramon Areces
- Subjects :
- 0301 basic medicine
Cytoplasm
Mitochondrial DNA
TIA1
Gene Expression
Apoptosis
Biology
Mitochondrion
Mitochondrial Dynamics
Poly(A)-Binding Proteins
OPA1
ELAV-Like Protein 1
GTP Phosphohydrolases
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Optic Atrophy, Autosomal Dominant
TIAR
Mitophagy
Gene expression
Autophagy
medicine
Humans
RNA, Messenger
Molecular Biology
Cell Proliferation
Mitochondrial spatial dynamics
Gene knockdown
Cell Biology
medicine.disease
Molecular biology
Mitochondria
T-Cell Intracellular Antigen-1
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
Mitochondrial Membranes
HuR
Optic Atrophy 1
Intracellular
Research Article
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....bcab9725b29aaeb14942f5f65823a2f4