A Role of P300 in Post-natal Cardiac Mitochondrial Gene Expression and Function

2006 ◽  
Vol 12 (8) ◽  
pp. S162-S163
Author(s):  
Yasuaki Nakagawa ◽  
Koichiro Kuwahara ◽  
Masaki Harada ◽  
Genzo Takemura ◽  
Masaharu Akao ◽  
...  
Author(s):  
Danielle E. Levitt ◽  
Tekeda F Ferguson ◽  
Stefany DePrato Primeaux ◽  
Jeanette A Zavala ◽  
Jameel Ahmed ◽  
...  

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53±9 yrs, body mass index: 29.0±6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information (Alcohol Use Disorders Identification Test, AUDIT), then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (p<0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, non-mitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.


Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 757-760 ◽  
Author(s):  
Ronald A. Butow ◽  
Hong Zhu ◽  
Philip Perlman ◽  
Heather Conrad-Webb

All mRNAs on the yeast mitochondrial genome terminate at a conserved dodecamer sequence 5′-AAUAAUAUUCUU-3′. We have characterized two mutants with altered dodecamers. One contains a deletion of the dodecamer at the end of the var1 gene, and the other contains two adjacent transversions in the dodecamer at the end of the reading frame of fit1, a gene within the ω+ allele of the 21S rRNA gene. In each mutant, expression of the respective gene is blocked completely. A dominant nuclear suppressor, SUV3-1, was isolated that suppresses the var1 deletion but is without effect on the fit1 dodecamer mutations. Unexpectedly, however, we found that SUV3-1 blocks expression of the wild-type fit1 allele by blocking processing at its dodecamer. SUV3-1 has pleiotropic effects on mitochondrial gene expression, affecting RNA processing, RNA stability, and translation. Our results suggest that RNA metabolism and translation may be part of a multicomponent complex within mitochondria.Key words: mitochondria, yeast, mRNA, RNA processing, 3′ dodecamer.


2001 ◽  
Vol 1 (S1) ◽  
Author(s):  
H van der Spek ◽  
M Siep ◽  
L de Jong ◽  
SDJ Elzinga ◽  
K van Oosterum ◽  
...  

2001 ◽  
Vol 54 ◽  
pp. S11-S27 ◽  
Author(s):  
Carolyn D Berdanier ◽  
Helen B Everts ◽  
Christina Hermoyian ◽  
Clayton E Mathews

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 671-671
Author(s):  
Xiaomin Zhang ◽  
Fathima Ameer ◽  
Jasmine Crane ◽  
Gohar Azhar ◽  
Jeanne Wei

Abstract Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. Alternatively spliced isoforms may lose part of the protein domain and have different intracellular localization as well as distinct functions. The main form of the SIRT1 (SIRT1v1) protein contains 11 exons. We have identified two new isoforms, SIRT1v2 (lost 2 exons), and SIRT1v3 (lost 3 exons), but their effect on mitochondrial gene expression has not been reported. To study the effect of the three SIRT1 isoforms on mitochondrial gene expression and function, neuronal cells were transfected with SIRT1 isoforms v1, v2 or v3 plasmids, respectively. Gene expression was measured by quantitative reverse transcription PCR (RT-qPCR). Our data showed SIRT1 isoforms v1, v2 and v3 differentially regulated PCG-1alpha and PCG-1beta, which are the upstream regulators of mitochondrial structure and function. SIRT1v1 upregulated mitofusin-1 (MFN1), the mitochondrial dynamin-like GTPase (OPA1) gene, and the transcription factor A mitochondrial (TFAM) gene. In contrast, the SIRT1-v2 isoform repressed the MFN1, MFN2, and TFAM genes, while the SIRT1-v3 isoform repressed the MFN1 gene. In addition, the three SIRT1 isoforms differentially affected the mitochondrial respiratory complex I genes, including NDUFAB1, NDUFS1, NDUFV1, NDUFV2. The data indicates that SIRT1 regulates mitochondrial biogenesis and function through a signaling pathway involving PGC-1alpha, PCG-1beta, mitofusin 1 and 2, OPA1, and TFAM genes. Taken together, alternative splicing generated three SIRT1 isoform proteins with diverse functions. Age-related changes in the alternative splicing events are likely to impact sirtuin-regulated cellular functions and signaling pathways in aging and senescence.


Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 29
Author(s):  
Jennifer D. Sisler ◽  
Magdalena Szelag ◽  
Ramesh Potla ◽  
Qifang Zhang ◽  
Karol Szczepanek ◽  
...  

2009 ◽  
Vol 284 (28) ◽  
pp. 18624-18633 ◽  
Author(s):  
Sandra Kleiner ◽  
Van Nguyen-Tran ◽  
Olivia Baré ◽  
Xueming Huang ◽  
Bruce Spiegelman ◽  
...  

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