scholarly journals Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

2017 ◽  
Vol 18 (4) ◽  
pp. 786 ◽  
Author(s):  
Nasra Yasin ◽  
Leo Veenman ◽  
Sukhdev Singh ◽  
Maya Azrad ◽  
Julia Bode ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Gene ◽  
Retrograde Signaling ◽  
Nuclear Gene Expression ◽  
Mitochondrial Retrograde Signaling

scholarly journals HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Manti Guha ◽  
Satish Srinivasan ◽  
Kip Guja ◽  
Edison Mejia ◽  
Miguel Garcia-Diaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Transcriptional Activation ◽  
Nuclear Gene ◽  
C2c12 Cells ◽  
Retrograde Signaling ◽  
Epigenetic Mechanism ◽  
Mitochondrial Stress ◽  
Nuclear Gene Expression ◽  
Mitochondrial Dna Copy Number

Abstract Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced transcription coactivator hnRNAP2 acetylates Lys 8 of H4 through an intrinsic histone lysine acetyltransferase (KAT) activity with Arg 48 and Arg 50 of hnRNAP2 being essential for acetyl-CoA binding and acetyltransferase activity. H4K8 acetylation at the mitochondrial stress-responsive promoters by hnRNAP2 is essential for transcriptional activation. We found that the previously described mitochondria-to-nucleus retrograde signaling-mediated transformation of C2C12 cells caused an increased expression of genes involved in various oncogenic processes, which is retarded in hnRNAP2 silenced or hnRNAP2 KAT mutant cells. Taken together, these data show that altered gene expression by mitochondria-to-nucleus retrograde signaling involves a novel hnRNAP2-dependent epigenetic mechanism that may have a role in cancer and other pathologies.

scholarly journals The SAL-PAP Chloroplast Retrograde Pathway Contributes to Plant Immunity by Regulating Glucosinolate Pathway and Phytohormone Signaling

2017 ◽  
Vol 30 (10) ◽  
pp. 829-841 ◽  
Author(s):  
Yasuhiro Ishiga ◽  
Mutsumi Watanabe ◽  
Takako Ishiga ◽  
Takayuki Tohge ◽  
Takakazu Matsuura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Pseudomonas Syringae ◽  
Expression Profiles ◽  
Plant Immunity ◽  
Gene Expression Profiles ◽  
Nuclear Gene ◽  
Retrograde Signaling ◽  
Necrotrophic Pathogen ◽  
Nuclear Gene Expression

Chloroplasts have a crucial role in plant immunity against pathogens. Increasing evidence suggests that phytopathogens target chloroplast homeostasis as a pathogenicity mechanism. In order to regulate the performance of chloroplasts under stress conditions, chloroplasts produce retrograde signals to alter nuclear gene expression. Many signals for the chloroplast retrograde pathway have been identified, including chlorophyll intermediates, reactive oxygen species, and metabolic retrograde signals. Although there is a reasonably good understanding of chloroplast retrograde signaling in plant immunity, some signals are not well-understood. In order to understand the role of chloroplast retrograde signaling in plant immunity, we investigated Arabidopsis chloroplast retrograde signaling mutants in response to pathogen inoculation. sal1 mutants (fry1-2 and alx8) responsible for the SAL1-PAP retrograde signaling pathway showed enhanced disease symptoms not only to the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000 but, also, to the necrotrophic pathogen Pectobacterium carotovorum subsp. carotovorum EC1. Glucosinolate profiles demonstrated the reduced accumulation of aliphatic glucosinolates in the fry1-2 and alx8 mutants compared with the wild-type Col-0 in response to DC3000 infection. In addition, quantification of multiple phytohormones and analyses of their gene expression profiles revealed that both the salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling pathways were down-regulated in the fry1-2 and alx8 mutants. These results suggest that the SAL1-PAP chloroplast retrograde pathway is involved in plant immunity by regulating the SA- and JA-mediated signaling pathways.

scholarly journals Mitochondrial TSPO Deficiency Triggers Retrograde Signaling in MA-10 Mouse Tumor Leydig Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 252
Author(s):  
Jinjiang Fan ◽  
Vassilios Papadopoulos
Keyword(s):  
Gene Expression ◽  
Membrane Potential ◽  
Intracellular Signaling ◽  
Leydig Cells ◽  
Expression Profiles ◽  
Nuclear Gene ◽  
Retrograde Signaling ◽  
Mouse Tumor ◽  
Nuclear Gene Expression ◽  
Indel Mutation

The mitochondrial translocator protein (TSPO) has been shown to bind cholesterol with high affinity and is involved in mediating its availability for steroidogenesis. We recently reported that targeted Tspo gene deletion in MA-10 mouse tumor Leydig cells resulted in reduced cAMP-stimulated steroid formation and significant reduction in the mitochondrial membrane potential (ΔΨm) compared to control cells. We hypothesized that ΔΨm reduction in the absence of TSPO probably reflects the dysregulation and/or maintenance failure of some basic mitochondrial function(s). To explore the consequences of TSPO depletion via CRISPR-Cas9-mediated deletion (indel) mutation in MA-10 cells, we assessed the transcriptome changes in TSPO-mutant versus wild-type (Wt) cells using RNA-seq. Gene expression profiles were validated using real-time PCR. We report herein that there are significant changes in nuclear gene expression in Tspo mutant versus Wt cells. The identified transcriptome changes were mapped to several signaling pathways including the regulation of membrane potential, calcium signaling, extracellular matrix, and phagocytosis. This is a retrograde signaling pathway from the mitochondria to the nucleus and is probably the result of changes in expression of several transcription factors, including key members of the NF-κB pathway. In conclusion, TSPO regulates nuclear gene expression through intracellular signaling. This is the first evidence of a compensatory response to the loss of TSPO with transcriptome changes at the cellular level.

scholarly journals Coordination of Plastid Protein Import and Nuclear Gene Expression by Plastid-to-Nucleus Retrograde Signaling

2009 ◽  
Vol 151 (3) ◽  
pp. 1339-1353 ◽  
Author(s):  
Tomohiro Kakizaki ◽  
Hideo Matsumura ◽  
Katsuhiro Nakayama ◽  
Fang-Sik Che ◽  
Ryohei Terauchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Import ◽  
Nuclear Gene ◽  
Retrograde Signaling ◽  
Nuclear Gene Expression ◽  
Plastid Protein

Chloroplast Redox Control of Nuclear Gene Expression—A New Class of Plastid Signals in Interorganellar Communication

2003 ◽  
Vol 5 (1) ◽  
pp. 95-101 ◽  
Author(s):  
Thomas Pfannschmidt ◽  
Katia Schütze ◽  
Vidal Fey ◽  
Irena Sherameti ◽  
Ralf Oelmüller
Keyword(s):  
Gene Expression ◽  
Nuclear Gene ◽  
Redox Control ◽  
New Class ◽  
Nuclear Gene Expression
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