Deficiency of T-Cell Intracellular Antigen 1 in Murine Embryonic Fibroblasts Is Associated with Changes in Mitochondrial Morphology and Respiration.

Isabel Carrascoso,Beatriz Ramos Velasco,José M Izquierdo

doi:10.3390/ijms222312775

Abstract

T-cell intracellular antigen 1 (TIA1) is a multifunctional RNA-binding protein involved in regulating gene expression and splicing during development and in response to environmental stress, to maintain cell homeostasis and promote survival. Herein, we used TIA1-deficient murine embryonic fibroblasts (MEFs) to study their role in mitochondria homeostasis. We found that the loss of TIA1 was associated with changes in mitochondrial morphology, promoting the appearance of elongated mitochondria with heterogeneous cristae density and size. The proteomic patterns of TIA1-deficient MEFs were consistent with expression changes in molecular components related to mitochondrial dynamics/organization and respiration. Bioenergetics analysis illustrated that TIA1 deficiency enhances mitochondrial respiration. Overall, our findings shed light on the role of TIA1 in mitochondrial dynamics and highlight a point of crosstalk between potential pro-survival and pro-senescence pathways.

Highlights

The RNA-binding protein (RBP) T-cell intracellular antigen 1 (TIA1) is involved in many aspects of RNA metabolism and governs the flow of gene expression [1,2]
Immunostaining of lysosomal-associated membrane protein 1 (LAMP-1, middle panel), a glycoprotein used as a lysosomal marker, showed an increase in the number of lysosomes in TIA1 knock out (TIA1-KO) mouse embryonic fibroblasts (MEFs) (Figure 1, middle panel), which agrees with previous findings [21]
We found that TIA1-KO MEFs had an increase in the number of mitochondrial DNA copies measured as the ratio of mitochondrial/nuclear DNA, which may be the result of a decrease in mitochondrial fission and/or an increase in mitochondrial fusion [21]

Summary

Introduction

The RNA-binding protein (RBP) T-cell intracellular antigen 1 (TIA1) is involved in many aspects of RNA metabolism and governs the flow of gene expression [1,2]. TIA1 is a master regulator of the crosstalk between nuclear and cytoplasmic compartments in eukaryotic cells [1,2]. It modulates both constitutive and alternative splicing [6,7,8], aids in the transport and subcellular localization of mRNAs [9,10,11] and is responsible for the stability and translation of mRNAs [12,13,14,15,16] by direct interaction or competition with other proteins and RNAs [16,17,18,19,20]. It is thought that TIA1 interacts potentially with 5–10% of the coding and non-coding genes of proteins that are synthesized from the human genome [18,19,20]

Methods

Results

Conclusion