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

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.

The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease

“…Mitochondria respond to changes in genetic, metabolic and/or environmental conditions by modifying the dynamics of their morphology and architecture to achieve cellular homeostasis or to initiate mitophagy and/or cell death or apoptosis. TIA1 has been associated with mitochondrial respiration and mitochondrial fission/fusion dynamics [43,88,[92][93][94]119]. Mitochondrial respiration is linked to TIA1 expression [43,92,94,119].…”

“…TIA1 has been associated with mitochondrial respiration and mitochondrial fission/fusion dynamics [43,88,[92][93][94]119]. Mitochondrial respiration is linked to TIA1 expression [43,92,94,119]. Indeed, TIA1 directly regulates the translation of cytochrome c mRNA [43].…”

“…Indeed, TIA1 directly regulates the translation of cytochrome c mRNA [43]. Deletion or reduction of TIA1 leads to the accumulation of elongated mitochondria [88,94,119]. Conversely, overexpression of TIA1 favors mitochondrial clustering and division/fission [92][93][94].…”

“…Conversely, overexpression of TIA1 favors mitochondrial clustering and division/fission [92][93][94]. The function of TIA1 also appears to be associated with translation of mitochondrial fission factor (MFF) through competition with miRNA-27 to bind to the 3 UTR [94], as well as with OPA1 expression through alternative splicing and differential processing of its isoforms [92,119] (Figures 5 and 6).…”