GLTSCR2/PICT1 links mitochondrial stress and Myc signaling

Yoon, John C.; Ling, Alvin J. Y.; Isik, Meltem; Lee, Dong-Young Donna; Steinbaugh, Michael J.; Sack, Laura; Boduch, Abigail N.; Blackwell, T. Keith; Sinclair, David A.; Elledge, Stephen J.

doi:10.1073/pnas.1400705111

Cited by 15 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical relevance was obtained from OMIM and PubMed, both for animal model and human. Table references (superscript numbers): (1) Yoon et al., ; (2) Yang et al., ; (3) Myers et al., ; (4) Estrada et al., . *Not in Interactome.…”

Section: Resultsmentioning

confidence: 99%

Genomic and phenotypic signatures of climate adaptation in an Anolis lizard

Rodríguez

Rusciano

Hamilton

et al. 2017

Ecology and Evolution

View full text Add to dashboard Cite

Integrated knowledge on phenotype, physiology, and genomic adaptations is required to understand the effects of climate on evolution. The functional genomic basis of organismal adaptation to changes in the abiotic environment, its phenotypic consequences, and its possible convergence across vertebrates are still understudied. In this study, we use a comparative approach to verify predicted gene functions for vertebrate thermal adaptation with observed functions underlying repeated genomic adaptations in response to elevation in the lizard Anolis cybotes. We establish a direct link between recurrently evolved phenotypes and functional genomics of altitude‐related climate adaptation in three highland and lowland populations in the Dominican Republic. We show that across vertebrates, genes contained in this interactome are expressed within the brain, the endocrine system, and during development. These results are relevant to elucidate the effect of global climate change across vertebrates and might aid in furthering insight into gene–environment relationships under disturbances to homeostasis.

show abstract

Section: Resultsmentioning

confidence: 99%

Genomic and phenotypic signatures of climate adaptation in an Anolis lizard

Rodríguez

Rusciano

Hamilton

et al. 2017

Ecology and Evolution

View full text Add to dashboard Cite

show abstract

“…The mammalian SKN-1 homolog Nrf2 is also known to play a role in mitochondrial biogenesis. When overexpressed Nrf2 was shown to be a negative modulator of mitochondrial mass and membrane potential in a high throughput screen using C2C12 myoblast cells [73]. However, when upregulated under physiological conditions Nrf2 was found to be a positive regulator of mitochondrial biogenesis by inducing nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression in heart [74], liver [75], and lung [76].…”

Section: Discussionmentioning

confidence: 99%

D-beta-hydroxybutyrate extends lifespan in C. elegans

Edwards

Canfield

Copes

et al. 2014

Aging

156

129

View full text Add to dashboard Cite

The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan of C. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated βHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and βHB dehydrogenase activity induced by βHB addition, suggesting that F55E10.6 functions as an inducible βHB dehydrogenase. Furthermore, βHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-βHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways.

show abstract

“…A reduction in mitochondrial membrane potential is an early indicator of apoptosis induction [16]. Cardiomyoblast apoptosis was detected using MitoCapture mitochondrial apoptosis kit according to the protocol provided by the manufacturer [17,18].…”

Section: Methodsmentioning

confidence: 99%

Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of Histone Deacetylase 4

et al. 2016

View full text Add to dashboard Cite

Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml). Cell cytotoxicity, apoptosis, mitochondrial respiration, and mitochondrial permeability transition pore (mPTP) were determined. Western blotting was employed to determine active-caspase 3, annexin V, and HDAC4 expression. As compared to wild type H9c2 group, HDAC4 overexpression remarkably led to a great increase in cell death as evident by the increased lactate dehydrogenase (LDH) leakage, ratio of caspase-3-positive cells as well as the upregulated levels of active-caspase 3 and annexin V shown by western blot analysis. In addition, HDAC4 overexpression also induced much severe mitochondrial dysfunction, as indicated by apoptotic mitochondria and increased mPTP. However, irisin treatment significantly attenuated all of these effects. Though irisin treatment did not influence the expression of HDAC4 at the transcriptional level, western blot analysis showed that HDAC4 protein levels decreased in a time-dependent way after administration of irisin, which is associated with the degradation of HDAC4 mediated by small ubiquitin-like modification (SUMO). Our results are the first to demonstrate that the protective effects of irisin in cardiomyoblasts exposed to hypoxia/reoxygenation might be associated with HDAC4 degradation.

show abstract

GLTSCR2/PICT1 links mitochondrial stress and Myc signaling

Cited by 15 publications

References 33 publications

Genomic and phenotypic signatures of climate adaptation in an Anolis lizard

Genomic and phenotypic signatures of climate adaptation in an Anolis lizard

D-beta-hydroxybutyrate extends lifespan in C. elegans

Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of Histone Deacetylase 4

Contact Info

Product

Resources

About