Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use

2021 ◽  
Author(s):  
Danielle E. Levitt ◽  
Tekeda F Ferguson ◽  
Stefany DePrato Primeaux ◽  
Jeanette A Zavala ◽  
Jameel Ahmed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Use ◽  
Glucose Tolerance ◽  
Mitochondrial Gene ◽  
Proton Leak ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Volume ◽  
And Function ◽  
The Relationship

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.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
And Function

scholarly journals Sirtuin-1 isoforms differentially regulate mitochondrial function

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 671-671
Author(s):  
Xiaomin Zhang ◽  
Fathima Ameer ◽  
Jasmine Crane ◽  
Gohar Azhar ◽  
Jeanne Wei
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mitochondrial Gene ◽  
Intracellular Localization ◽  
Sirtuin 1 ◽  
Protein Domain ◽  
Mitochondrial Gene Expression ◽  
Age Related ◽  
And Function ◽  
Mitofusin 1

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.

scholarly journals PPARδ Agonism Activates Fatty Acid Oxidation via PGC-1α but Does Not Increase Mitochondrial Gene Expression and Function

2009 ◽  
Vol 284 (28) ◽  
pp. 18624-18633 ◽  
Author(s):  
Sandra Kleiner ◽  
Van Nguyen-Tran ◽  
Olivia Baré ◽  
Xueming Huang ◽  
Bruce Spiegelman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Gene ◽  
Acid Oxidation ◽  
Mitochondrial Gene Expression ◽  
And Function

Is mitochondrial gene expression coordinated or stochastic?

2018 ◽  
Vol 46 (5) ◽  
pp. 1239-1246 ◽  
Author(s):  
Richard G. Lee ◽  
Danielle L. Rudler ◽  
Oliver Rackham ◽  
Aleksandra Filipovska
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
De Novo ◽  
Rna Binding Proteins ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
Energy Demands ◽  
Multiple Processes ◽  
Coordinated Expression ◽  
And Function

Mitochondrial biogenesis is intimately dependent on the coordinated expression of the nuclear and mitochondrial genomes that is necessary for the assembly and function of the respiratory complexes to produce most of the energy required by cells. Although highly compacted in animals, the mitochondrial genome and its expression are essential for survival, development, and optimal energy production. The machinery that regulates gene expression within mitochondria is localised within the same compartment and, like in their ancestors, the bacteria, this machinery does not use membrane-based compartmentalisation to order the gene expression pathway. Therefore, the lifecycle of mitochondrial RNAs from transcription through processing, maturation, translation to turnover is mediated by a gamut of RNA-binding proteins (RBPs), all contained within the mitochondrial matrix milieu. Recent discoveries indicate that multiple processes regulating RNA metabolism occur at once but since mitochondria have a new complement of RBPs, many evolved de novo from nuclear genes, we are left wondering how co-ordinated are these processes? Here, we review recently identified examples of the co-ordinated and stochastic processes that govern the mitochondrial transcriptome. These new discoveries reveal the complexity of mitochondrial gene expression and the need for its in-depth exploration to understand how these organelles can respond to the energy demands of the cell.

Abstract 892: Doxorubicin-induced cardiotoxicity in iPSC-cardiomyocytes: Altered mitochondrial gene expression and function

2018 ◽  
Author(s):  
Monica E. Reyes ◽  
Rashida Callender ◽  
Jianzhong Ma ◽  
Megan L. Grove ◽  
Alanna C. Morrison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
And Function
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