Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise

Joseph, Anna‐Maria; Pilegaard, Henriette; Litvintsev, Anastassia; Leick, Lotte; Hood, David A.

doi:10.1042/bse0420013

Cited by 103 publications

(94 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The therapeutic effects of endurance exercise are associated with the maintenance of homeostatic energy metabolism via mitochondrial biogenesis in various tissues including skeletal muscle, heart, brain, adipose tissue, and liver (2)(3)(4). Endurance exercise-mediated enhancement of skeletal muscle mitochondrial content and oxidative capacity is a well established phenomenon in physiology (3), yet the molecular mechanisms promoting this process have only recently begun to be unraveled (5).…”

mentioning

confidence: 99%

Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis

Safdar

Little

Stokl

et al. 2011

Journal of Biological Chemistry

284

221

View full text Add to dashboard Cite

Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor ␥ co-activator 1␣ (PGC-1␣). PGC-1␣ regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1␣ has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1␣ remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1␣ content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n ‫؍‬ 12/group; Ǩ ‫؍‬ () were randomly assigned to sedentary (SED), forced-endurance (END) exercise (15 m/min for 90 min), or forced endurance ؉3 h of recovery (END؉3h) group. The END group was sacrificed immediately after exercise, whereas the SED and END؉3h groups were euthanized 3 h after acute exercise. Acute exercise coordinately increased the mRNA expression of nuclear and mitochondrial DNAencoded mitochondrial transcripts. Nuclear and mitochondrial abundance of PGC-1␣ in END and END؉3h groups was significantly higher versus SED mice. In mitochondria, PGC-1␣ is in a complex with mitochondrial transcription factor A at mtDNA D-loop, and this interaction was positively modulated by exercise, similar to the increased binding of PGC-1␣ at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1␣ re-localizes into nuclear and mitochondrial compartments where it functions as a transcriptional co-activator for both nuclear and mitochondrial DNA transcription factors. These results suggest that PGC-1␣ may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis.Physical inactivity is a major threat to public health worldwide. It is a primary modifiable risk factor for sarcopenia, cardiovascular diseases, type 2 diabetes, obesity, stroke, hypertension, and other chronic diseases including colon and breast cancer, end-stage renal disease, osteoporosis, osteoarthritis, and neuromuscular and neurometabolic disorders (1). Given the dire consequences associated with sedentary living, public health initiatives and therapeutic strategies that improve independent living and promote a physically active lifestyle are an international priority. Indeed, there is incontrovertible evidence from epidemiological studies and randomized trials that illustrate that regular physical activity and endurance exercise reduces the risk of chronic diseases and physical disability in later life and even extends lifespan (1, 2). The therapeutic effects of endurance exercise are associated with the maintenance of homeostatic energy metabolism via mitochondrial biogenesis in various tissues including skeletal muscle, heart, brain, adipose tissue, and liver (2-4). Endurance exercise-mediated enhancement of skeletal muscle mitochondrial content and oxidative capacity is a well established phenomenon in physio...

show abstract

mentioning

confidence: 99%

Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis

Safdar

Little

Stokl

et al. 2011

Journal of Biological Chemistry

284

221

View full text Add to dashboard Cite

show abstract

“…PGC-1␣ has been suggested to be an important factor in regulating exercise training-induced adaptations in mitochondrial proteins (10,16,30). Nevertheless, a recent study from our laboratory using whole body PGC-1␣-KO mice demonstrated that PGC-1␣ is redundant in training-induced increases in expression of several mitochondrial proteins in skeletal muscles of young mice (18).…”

Section: Discussionmentioning

confidence: 98%

PGC-1α is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle

Leick

Fentz

Biensø

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, overexpression of Kif5b in C2C12 cells led to an increase of mitochondrial fluorescence. It has been shown that exercise training leads to mitochondrial biogenesis by altering the rates of PGC-1␣ and Tfam expression, modifying mitochondrial fission and fusion mechanisms and influencing the import of nuclear-derived gene products into the mitochondrion (16). We therefore measured cytochrome B by semiquantitative real-time PCR to evaluate the effects of Kif5b on mitochondrial biogenesis.…”

Section: Discussionmentioning

confidence: 99%

KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise

Argyropoulos

Stütz

Ilnytska

et al. 2009

Physiological Genomics

View full text Add to dashboard Cite

A genome-wide linkage scan for endurance training-induced changes in stroke volume detected a quantitative trait locus on chromosome 10p11 in white families of the HERITAGE Family Study. Dense microsatellite mapping narrowed down the linkage region to a 7 Mb area containing 16 known and 14 predicted genes. Association analyses with 90 single nucleotide polymorphisms (SNPs) provided suggestive evidence (P values from 0.03 to 0.06) for association in the kinesin heavy chain (KIF5B) gene locus in the whole cohort. The associations at the KIF5B locus were stronger (P values from 0.001 to 0.008) when the analyses were performed on linkage-informative families only (family-specific logarithm of the odds ratio scores Ͼ0.025 at peak linkage location). Resequencing the coding and regulatory regions of KIF5B revealed no new exonic SNPs. However, the putative promoter region was particularly polymorphic, containing eight SNPs with at least 5% minor allele frequency within 1850 bp upstream of the start codon. Functional analyses using promoter haplotype reporter constructs led to the identification of sequence variants that had significant effects on KIF5B promoter activity. Analogous inhibition and overexpression experiments showed that changes in KIF5B expression alter mitochondrial localization and biogenesis in a manner that could affect the ability of the heart to adjust to regular exercise. Our data suggest that KIF5B is a strong candidate gene for the response of stroke volume to regular exercise. Furthermore, training-induced changes in submaximal exercise stroke volume may be due to mitochondrial function and variation in KIF5B expression as determined by functional SNPs in its promoter.genotype; exercise training; functional studies; mitochondria REGULAR EXERCISE HAS BEEN shown to protect against morbidity and mortality from cardiovascular diseases (CVD), whereas sedentariness is associated with increased risk of CVD. Cardioprotective effects of exercise are mediated by several physiological mechanisms, such as improved plasma lipid and lipoprotein profile, lower blood pressure, improved endothelial function, and enhanced insulin sensitivity. Regular exercise also improves cardiac function. Exercise-trained hearts work more efficiently, i.e., physically active individuals have lower heart rates but greater stroke volume at rest and during submaximal exercise than their sedentary counterparts. Exercisetrained hearts can also adjust better to suddenly increased circulatory demands and tolerate better the demands of heavy physical exertion.Although regular physical activity improves cardiac function on average, there are marked interindividual differences in exercise training-induced changes in cardiac phenotypes. For instance, in the HERITAGE Family Study, a 20-wk endurance training program resulted in a mean increase of 3.9 ml/beat in stroke volume measured during steady-state exercise at 50 W (SV50) (29). However, the training responses ranged from a decrease of 41 ml/beat to an increase of 45 ml/beat. The stronge...

show abstract

Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise

Cited by 103 publications

References 31 publications

Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis

Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis

PGC-1α is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle

KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise

Contact Info

Product

Resources

About