Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes

Zamora, Mónica; Pardo, Rosario; Villena, Josep A.

doi:10.1016/j.bcp.2015.06.032

Cited by 31 publications

(15 citation statements)

References 179 publications

(225 reference statements)

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“…However, the studies reported here, together with our recent characterization of GPS2 role in regulating insulin signaling , add to the significance of GPS2 in the adipose tissue suggesting that it might serves a more general function in integrating the regulation of lipids mobilization from TG storage with their utilization via mitochondrial oxidative metabolism. As therapeutic and lifestyle interventions designed for improving insulin sensitivity often rely on increased mitochondria biogenesis and oxidative metabolism (Hu and Liu, 2011;Kusminski and Scherer, 2012;Newsholme et al, 2012;Patti and Corvera, 2010;Zamora et al, 2015), unraveling the molecular mechanisms regulating mitochondria biogenesis and function in response to energetic and metabolic demands is not only important for our basic understanding of cell biological processes, but also have the potential of leading to the development of novel therapeutic approaches for obese and diabetic patients. (E) Reduced mitochondrial protein content in BAT isolated from GPS2-AKO compared to WT littermates mice.…”

Section: Discussionmentioning

confidence: 99%

GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes

Cardamone

Tanasă

Cederquist

et al. 2017

Preprint

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2 SummaryAs most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. Together, these findings reveal an unexpected layer of regulation of mitochondrial gene transcription as they uncover a novel mitochondrianuclear communication pathway.

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Section: Discussionmentioning

confidence: 99%

GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes

Cardamone

Tanasă

Cederquist

et al. 2017

Preprint

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“…In fact, increasing mitochondrial biogenesis by pharmacological agents has been proposed as a potential therapeutic strategy for the treatment of insulin resistance and T2D [151, 152]. Nevertheless, a number of type 1 and type 2 diabetic mouse models show significantly increased mitochondrial area and number in the heart, which is accompanied by increased PGC-1α expression and mtDNA content, suggesting an enhanced mitochondrial biogenesis in the diabetic hearts[22, 24, 25, 145, 153].…”

Section: Mitochondrial Biogenesis In the Diabetic Heartmentioning

confidence: 99%

Mitochondrial quality control in the diabetic heart

Liang

Kobayashi

2016

Journal of Molecular and Cellular Cardiology

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Diabetes is a well known risk factor for heart failure. Diabetic heart damage is closely related to mitochondrial dysfunction and increased ROS generation. However, clinical trials have shown no effects of antioxidant therapies on heart failure in diabetic patients, suggesting that simply antagonizing existing ROS by antioxidants is not sufficient to reduce diabetic cardiac injury. A potentially more effective treatment strategy may be to enhance the overall capacity of mitochondrial quality control to maintain a pool of healthy mitochondria that are needed for supporting cardiac contractile function in diabetic patients. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission and fusion, mitophagy and biogenesis. The mitochondrial damage consistently observed in the diabetic hearts indicates a failure of the mitochondrial quality control mechanisms. Recent studies have demonstrated a crucial role for each of these mechanisms in cardiac homeostasis and have begun to interrogate the relative contribution of insufficient mitochondrial quality control to diabetic cardiac injury. In this review, we will present currently available literature that links diabetic heart disease to the dysregulation of major mitochondrial quality control mechanisms. We will discuss the functional roles of these mechanisms in the pathogenesis of diabetic heart disease and their potentials for targeted therapeutical manipulation.

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“…Maintenance of mitochondrial homeostasis through the balance of mitophagy, mitochondrial fission and fusion, and mitochondrial biogenesis is critical for tissue health (Palikaras & Tavernarakis, 2014). Impaired mitochondrial biogenesis plays a critical role in aging, neurodegeneration diseases, diabetes and cardiovascular diseases (Petersen, Dufour, Befroy, Garcia, & Shulman, 2004;Piao, Kim, Oh, & Pak, 2012;Ren, Pulakat, Whaley-Connell, & Sowers, 2010;Wang, Mascher, Psilander, Blomstrand, & Sahlin, 2011;Zamora, Pardo, & Villena, 2015). Cells do not generate mitochondria de novo, but instead stimulate healthy mitochondria to proliferate through mitochondrial biogenesis (Kowald & Kirkwood, 2011).…”

Section: Introductionmentioning

confidence: 99%

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

Deng

Zhang

et al. 2019

Journal of Food Science

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Several studies indicated that ginger (Zingiber officinale Roscoe) enhances thermogenesis and/or energy expenditure with which to interpret the beneficial effects of ginger on metabolic disorders. It is well known that mitochondrial activity plays an essential role in these processes. Thus, this study aimed to investigate the effect of ginger extract (GE) and its major components, 6‐gingerol and 6‐shogaol, on mitochondrial biogenesis and the underlying molecular mechanisms. Our results showed that GE at dose of 2 g/kg promoted oxygen consumption and intrascapular temperature in mice. The mitochondrial DNA (mtDNA) copy number in muscle and liver increased. Expression levels of oxidative phosphorylation (OXPHOS) related proteins and AMP‐activated protein kinase ɑ/proliferator‐activated receptor gamma coactivator 1 ɑ (AMPK/PGC1ɑ) signaling related proteins in the muscle, liver, and brown adipose tissue (BAT) increased as well. In HepG2 cells, GE at concentration of 2.5 and 5 mg/mL increased mitochondrial mass and mtDNA copy number. GE promoted ATP production, the activities of mitochondrial respiratory chain complex I and IV, and expression levels of OXPHOS complex related proteins and AMPK/PGC1ɑ signaling related proteins. The antagonist of AMPK eliminated partly the effect of GE on mitochondrial biogenesis. 6‐Gingerol increased mitochondrial mass, mtDNA copy number and ATP production, and the activities of mitochondrial respiratory chain complexes in HepG2 cells as well. However, both 6‐gingerol at high concentration of 200 µM and 6‐shogaol at 10 to 200 µM inhibited cell viability. In conclusion, GE promoted mitochondrial biogenesis and improved mitochondrial functions via activation of AMPK‐PGC1ɑ signaling pathway, and 6‐gingerol other than 6‐shogaol, may be the main active component. Practical Application Ginger (Zingiber officinale Roscoe) is a food seasoning and also used as a medical plant in alternative medicine throughout the world. Here, we demonstrated that ginger extract (GE) promoted mitochondrial biogenesis and mitochondrial function via activation of AMPK‐PGC1ɑ signaling pathway both in mice and in HepG2 cells, and 6‐gingerol may be its main active component. Ginger, with anticipated safety, is expected to be a long‐term used dietary supplement and be developed into a new remedy for mitochondrial dysfunctional disorders.

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Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes

Cited by 31 publications

References 179 publications

GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes

GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes

Mitochondrial quality control in the diabetic heart

Promotion of Mitochondrial Biogenesis via Activation of AMPK‐PGC1ɑ Signaling Pathway by Ginger (Zingiber officinale Roscoe) Extract, and Its Major Active Component 6‐Gingerol

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