Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

Abstract

BackgroundTid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.MethodsIn vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.ResultsExpression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/f mice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/f mice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/f mice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/f mice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.ConclusionTogether, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0443-8) contains supplementary material, which is available to authorized users.

HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling

“…Meanwhile, as expected, patients whose HNSCC tissue staining exhibited nuclear Galectin-7 staining had a poor survival compared to patients with cytoplasmic staining of Galectin-7 ( Figure 1 C ). To further determine the negative role of Tid1 in the modulation of Galectin-7 protein during head and neck cancer progression, keratinocyte-specific Tid1-deficient mice were generated by crossing Tid1 floxed mice (Tid1 flox/flox ) generated in our laboratory with tamoxifen-inducible cre-expressing transgenic mice driven by the K5 promoter 16 - 18 , 27 . 4NQO was added in the drinking water to induce tumors on the tongue surface of mice 28 .…”

“…Keratinocytes-specific Tid1-deficient mice were generated by breeding mice bearing a loxP-flanked Tid1 gene (Tid1 flox/flox ) with K5-Cre mice (generously provided by Dr. Chun-Ming Chen) 16 - 18 , 27 . The mice were injected intraperitoneally every other day for one week, starting at the age of 4 weeks, with either corn oil or 4-hydroxytamoxifen (4-5 mg/kg body weight) 27 .…”

“…In addition, Tid1 deficiency blocks early stage development of T cells 17 . Recently, we have shown that transgenic mice with muscle-specific Tid1 deletion display muscular dystrophic phenotype 18 . These results support the physiological roles and functions of Tid1 in cell survival and proliferation, and also provide the first evidence that co-chaperone protein is required for T cell and muscle development.…”

Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation

“…Additionally, Tid1 abrogates the Galectin-7/TCF3/MMP9 axis to repress the cancer metastasis [16]. We also report the participation of Tid1 in early embryogenesis [20], T cells development [21], muscular development and mitochondrial biogenesis [22] in normal development. We observe the elevation of Tid1 protein in differentiated C2C12 myoblast.…”

Redox Aspects of Chaperones in Cardiac Function

“…New chaperones have been discovered in the last years with multiple functions, as the small Tims chaperones, involved into the import and translocation of proteins and metabolites in the mitochondria, Tid1, a co-chaperone involved in mitochondrial homeostasis and cell apoptosis, and Hep1 that favors mtHSP70 folding and regulate mitochondrial proteostasis (Petrakis et al, 2009 ; Blamowska et al, 2012 ; Cheng et al, 2016 ). It is likely that new mitochondrial chaperones are still to be discovered.…”