LIX1-mediated changes in mitochondrial metabolism control the fate of digestive mesenchyme-derived cells

Guérin, Amandine; Angebault, Claire; Kinet, Sandrina; Cazevieille, Chantal; Rojo, Manuel; Fauconnier, Jérémy; Lacampagne, Alain; Mourier, Arnaud; Taylor, Naomi; Barbara, Pascal de Santa; Faure, Sandrine

doi:10.1016/j.redox.2022.102431

Cited by 7 publications

(8 citation statements)

References 70 publications

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“…Guérin A et al. once have reported that limb expression 1 (LIX1) downregulation alters mitochondrial quality control pathway to control the fate of digestive mesenchyme‐derived cells by regulating YAP1 and TAZ activity 36 . Here, we presented that YAP1 and TAZ can bind to mTORC1 to activate or inhibit the target genes in mitochondrial quality control pathway.…”

Section: Discussionmentioning

confidence: 70%

“…[33][34][35] Guérin A et al once have reported that limb expression 1 (LIX1) downregulation alters mitochondrial quality control pathway to control the fate of digestive mesenchyme-derived cells by regulating YAP1 and TAZ activity. 36 Here, we presented that YAP1 and TAZ can bind to mTORC1 to activate or inhibit the target genes in mitochondrial quality control pathway. Mitochondrial quality control plays a crucial role not only in modulating cellular activities and homeostasis but also ensuring mitochondrial proteome, such as high plasticity that let the adjustment of mitochondrial function to cellular and molecular requirements.…”

Section: Discussionmentioning

confidence: 98%

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circELP2 reverse‐splicing biogenesis and function as a pro‐fibrogenic factor by targeting mitochondrial quality control pathway

Zhang,

Tu,

Liu

et al. 2023

J Cellular Molecular Medi

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Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2‐medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR‐630 to increase transcriptional co‐activators Yes‐associated protein 1 (YAP1) and transcriptional co‐activator with PDZ‐binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR‐630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2‐miR‐630‐YAP1/TAZ‐mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2‐medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 98%

circELP2 reverse‐splicing biogenesis and function as a pro‐fibrogenic factor by targeting mitochondrial quality control pathway

Zhang,

Tu,

Liu

et al. 2023

J Cellular Molecular Medi

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“…It remains to understand how LIX1 controls MAPK reactivation in the presence of imatinib. LIX1 is localized in mitochondria, where it controls the shape of mitochondrial cristae and redox signaling [ 30 ]. It is well known that metabolic reprogramming is a hallmark of cancer cells to adapt to targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we focused on LImb eXpression 1 (LIX1), a protein that we previously identified as a regulator of digestive mesenchymal progenitor proliferation upstream of the Hippo transducers YAP1 and TAZ [ 28 ]. In GIST, LIX1 controls mitochondrial function, KIT protein level, ICC lineage specification through YAP1/TAZ, and cell proliferation [ 29 , 30 ]. Importantly, LIX1 expression is higher in patients with relapsed GIST [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

LIX1 Controls MAPK Signaling Reactivation and Contributes to GIST-T1 Cell Resistance to Imatinib

Ruiz-Demoulin

Trenquier

Dekkar

et al. 2023

IJMS

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Gastrointestinal stromal tumor (GIST), the most common sarcoma, is mainly caused by an oncogenic mutation in the KIT receptor tyrosine kinase. Targeting KIT using tyrosine kinase inhibitors, such as imatinib and sunitinib, provides substantial benefit; however, in most patients, the disease will eventually progress due to KIT secondary mutations leading to treatment failure. Understanding how GIST cells initially adapt to KIT inhibition should guide the selection of appropriate therapies to overcome the emergence of resistance. Several mechanisms have been broadly implicated in the resistance to imatinib anti-tumoral effects, including the reactivation of MAPK signaling upon KIT/PDGFRA targeted inhibition. This study provides evidence that LImb eXpression 1 (LIX1), a protein we identified as a regulator of the Hippo transducers YAP1 and TAZ, is upregulated upon imatinib or sunitinib treatment. LIX1 silencing in GIST-T1 cells impaired imatinib-induced MAPK signaling reactivation and enhanced imatinib anti-tumor effect. Our findings identified LIX1 as a key regulator of the early adaptative response of GIST cells to targeted therapies.

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“…Smooth muscle can undergo “phenotypic class switching,” with loss of contractile apparatus genes, increased expression of extracellular matrix proteins, increased proliferation, and increased cell mobility [ 32 , 33 ]. Phenotypic class switching is controlled in part by the putative RNA binding mitochondrial protein limb and CNS expressed 1 (LIX1), which is highly expressed in mesenchymal precursor cells able to differentiate into contractile smooth muscle [ 34 ]. LIX1 levels decline during the transition from precursor to contractile smooth muscle cells.…”

Section: Smooth Muscle Cell Biologymentioning

confidence: 99%

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting

Viti,

De Giorgio,

Ceccherini

et al. 2023

Dig Dis Sci

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Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype–phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first ‘European Forum on Visceral Myopathy’. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy. Graphical Abstract

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LIX1-mediated changes in mitochondrial metabolism control the fate of digestive mesenchyme-derived cells

Cited by 7 publications

References 70 publications

circELP2 reverse‐splicing biogenesis and function as a pro‐fibrogenic factor by targeting mitochondrial quality control pathway

circELP2 reverse‐splicing biogenesis and function as a pro‐fibrogenic factor by targeting mitochondrial quality control pathway

LIX1 Controls MAPK Signaling Reactivation and Contributes to GIST-T1 Cell Resistance to Imatinib

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting

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